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THE 



PRINCIPLES AND METHODS 



OF 



THERAPEUTICS 



By Adolphe Gubler, M. D., 

Professor of Therapeutics in the Faculty of Medicine, Paris, 

Member of the Academy of Medicine, Physician to 

the Beaujon Hospital, etc. 



TRANSLATED FROM THE FRENCH. 



PHILADELPHIA, Pa. 
D. G. Brinton, 115 South Seventh Street. 

1881. 






Y, V 



<# 



^ 
#- 



COPYRIGHT. 

D. G. BRINTON. 
1881. 



Press of Wm. F. Fell & Co., 
1220-1224 Sansom St., 
Philadelphia.. 






PREFATORY NOTE. 



The work here laid before the medical public differs so widely from other 
treatises in the language on Therapeutics, that a few words as to its scope will 
not be out of place. 

It is, as its title states, a discussion of the principles and the methods of thera- 
peutics. It does not take up this branch as an accessory to Materia Medica ; 
nor is it concerned, beyond a moderate extent, with the physiological action of 
drugs ; nor yet has it much to say on the treatment of individual diseases. 
These topics, which figure so prominently in most works on therapeutics, will 
be found to occupy comparatively little space in the present one. 

Professor Gubler chose to approach his subject from quite other directions 
and with other purposes. He aimed to represent, from the latest acquisitions 
of science, and by the aid of the most careful instructions, first, the methods 
which can be most effectively employed in the administration of remedial 
agents, and next the principles or processes by which their remedial action is 
exerted on the human economy. It is a study founded on clinical, physiologi- 
cal and chemical observations of the actions of medicines in disease, and the 
technical artifices for their introduction into the organism. 

Approached with this understanding, his lectures will be found most fruitful 
to the careful student. They will explain many apparent contradictions and 
obscurities which often puzzle and sometimes dishearten the practitioner. It 
is true that his style is at times involved, and his reasoning not always easy to 
follow ; but the labor to grasp his thought will certainly be found to be remu- 
nerative. 

The translation has been made by Dr. M. J. Halloran, a former pupil of the 
author, and Mr. Charles A. Poizat. The biographical sketch has been furnished 
by the former. 

The metric weights have usually been preserved in the text, as they are 
now familiar to American physicians. Their proximate values may, how- 
ever, here be added : 

1 milligramme,= ----- gr. -fa. 

1 centigramme,= ... - g r . J. 

1 gramme,= gr. xvss. 

1 kilo°:ramme,= lbs. ijss. 

1 centimetre,= T 4 <j of an inch. 



BIOGRAPHICAL SKETCH 

OF 

Professor Adolphe Gubler. 



M. Gubler, Professor of Therapeutics of the Faculty of Medicine of Paris, 
was one of the most remarkable figures in the modern French school of 
medicine. 

A worthy pnpil of Trousseau, he was at once an able clinical teacher and 
a distinguished botanist and chemist. His works, his teachings, his lectures 
on therapeutics, admirable as regards the doctrines inculcated and for their 
scientific value, placed him in the foremost rank among contemporary 
scientists. 

His real name was Goblet, and he was born at Metz, April 5th, 1821. His 
parents were in very moderate circumstances, and settled in a village near the 
Belgian frontier, where he attended school, and profited so well from his 
lessons that at the age of thirteen his masters had no more to teach him. 

An attack of pleurisy, brought on by submersion in a frozen pond, retarded 
his studies for a considerable period. On his recovery he was placed with an 
uncle, a druggist, at Rocroy. 

Here Gubler found, relegated to the topmost shelves of the library and 
covered with dust, various old books, which he examined with curiosity ; they 
were ancient treatises on botany, and among them he became particularly 
interested in the venerable " Traite de la Vcrtu des Plantes," by Guy de la 
Brosse, and the " Historia Generalis Plantarum" by Delechamps. 

A new life opened before him ; his days were passed in the fields, and in 
the evening he attempted to compare the specimens collected with the descrip- 
tions of his books. Soon recognizing their imperfections, he mapped out and 
created for himself a system of botany which was admired by teachers of 
eminence. He even wrote a monograph on mosses, which he subsequently 
destroyed, but which merited preservation for the accuracy in description and 
the high standard of the general views expressed by a youth of fifteen. 

In later years he recalled with grateful recollection the laborious yet happy 
period of his youth passed in the little village of Rocroy. A year later he 
was sent to school at Metz, where he terminated brilliantly his studies, and in 



6 BIOGRAPHICAL SKETCH OF 

1841 set out for Paris, poor in money but rich in hope, and sustained by an 
indomitable will. 

His success was marked and rapid. In 1844 he received the first prize at 
the Practical School, (dissections,) and in 1845 he was appointed interne in 
the Paris hospitals. It was at this period of his life that an accident, which 
nearly proved fatal, rendered his health, already delicate, still more pre- 
carious. 

Baudelocque one day asked Trousseau to select for him a distinguished 
interne, to accompany on his travels a young man of good family, who was in 
a state of extreme mental distress, brought on by participation in a duel. 
Trousseau immediately thought of Gubler, who refused to leave his studies 
until Trousseau desired it as a personal favor, when he acceded. All went well 
until they arrived at Milan. By the change of scene the young patient had 
almost regained his usual spirits. At Milan, however, he again thought him- 
self pursued by his enemies, and desired Gubler to occupy the same room 
with him. During the night he suffered very much from hallucinations, and 
Gubler was obliged to leave his bed to calm the patient. This he succeeded 
in doing, and was in the act of returning to his own bed, when he heard the 
click of a pistol ; he turned towards his patient, and received a bullet full in 
the chest ; he fell, and the maniac threw himself upon him, inflicting wounds 
of great gravity, with a knife, on the chest, neck and abdomen. Gubler was 
taken to the Milan hospital, where his recovery, at first very doubtful, was 
brought about, notwithstanding the penetrating wound of the chest and the 
development of peritonitis consecutive on the abdominal wounds. The cica- 
trices in the neck were of such extent that he was accustomed to wear his hair 
long to conceal them. 

He thus lost a year from his studies, for his convalescence was slow. The 
ball was never extracted, and he attributed to its presence many of the troubles 
from which he suffered in later years. 

In 1848 and 1849 his first memoirs, principally on botanical pathology ; on 
the development of galls ; on the tumors observed on apple trees ; on the 
existence of a new form of fungous growth in diseased olives, were presented 
to the Society of Biology, then newly founded. 

These were not isolated observations, without ultimate object ; Gubler intended 
them to form part of a work on comparative pathology, which he always 
intended to produce; indeed, throughout his works are many evidences how 
much this subject occupied his attention, as in his papers on the discovery of 
a growth in the mucus contained in bronchial dilatations ; observations on the 
diseases of fishes ; the anomalies observed in a case of hermaphrodism and 
exaggeration of size (geantisme) in the pisticia lentiscus. 

In his work on the origin and conditions favorable to the development of 
the oidium albicans, he showed that acidity of the saliva is a necessary condi- 
tion for the development of thrush (muguet), and that when the cryptogamous 
growth is fully developed, it renders the saliva acid, and also acts as a special 
ferment, at least for saccharine matters. He demonstrated also that the trans- 



PROF. ADOLPHE GUBLER. 7 

mission of this growth is a true transplantation ; that it is not a pathological 
product, but simply an epiphenomenon in the course of various affections 
which present in common digestive derangements, in conjunction with an 
abnormal condition of the buccal secretions. 

In a second memoir, Gubler combats, with striking arguments, the idea of 
indefinite transformation (evolution) put forward by Lamarck and Darwin, 
and shows himself a partisan of the relative fixity of the various, species of 
animal life. 

These researches entered but casually into his projects. He desired especi- 
ally to be known as a clinician, and he entered upon the study of clinical 
medicine with such ardor that within a year after receiving his degree he was 
appointed chief of clinics, and later, physician in the Paris hospitals, although 
it was his first concours. 

Two years later, in a brilliant concours for the agregation, he sustained his 
" Thesis on Cirrhosis," a work which has remained classic on the subject. In 
it he established the true theory of the malady ; the genesis of intestinal 
hemorrhage in diseases of the liver ; the history of the collateral circulation 
when the organ is profoundly affected and the distinction between the atrophic 
and hypertrophic forms of cirrhosis. 

From this r period Gubler commenced to realize the dreams of his youth. 
In 1852 he was elected Vice President of the Society of Biology ; in 1862 
and 1866 the Botanical Society did him the same honor ; in 1865 the Academy 
of Medicine elected him one of its members, and during the same year he was 
made chevalier of the Legion d'Honneur, for his services at the Beaujon 
Hospital during an epidemic of cholera. 

Finally, in 1868, he received the supreme reward of a life of scientific labor 
— he was made Professor of Therapeutics in the Paris Faculty of Medicine. 

Chemistry, pharmacy, natural history physiology, . pathology, anatomy, all 
sciences in which he was deeply learned, served to render his lectures 
extremely interesting and brilliant, and aided much in the new impetus given 
by him to the science of therapeutics. 

Later, when the Academy of Sciences decreed to him the Chaussier prize 
for his great work, " Commentaires Therapeutiques sur le Codex" his friends 
urged him as candidate for the Institute, and twice in succession the section 
of medicine and surgery of this learned body presented him at the head of 
their list of candidates. 

The list of M. Gubler's works is very extensive, and many of them have 
taken rank in science as definitive discoveries : as his inaugural thesis on the 
functions and pathology of Mery's glands ; his memoirs on the existence of 
muciparous glands in the gall-bladder, demonstrating the contractility of the 
veins ; on the presence of sugar in the lymph, which he asserted contained 
also normally incomplete blood corpuscles — whence the doctrines at present 
received regarding the part played by the lymphatic system in blood forma- 
tion. 

He studied also the lacteal secretion observed in newly-born children, and 



i 



8 BIOGRAPHICAL SKETCH OF 

the physiology of sleep, founded on the existence of a static hyperemia of the 
brain. 

In applied chemistry his labors have been of equal importance. He demon- 
strated the alkalinity of the urine during convalescence ; the transitory glyco- 
suria of the period of reaction in cholera ; the passage and diagnosis of the 
biliary resins in true hepatic jaundice ; finally, the discovery of the chemical 
properties and clinical signification of the presence of indican, or indigose, in 
the urine. He established also the possibility of distinguishing, by examina- 
tion of the urine, between true inflammatory and malignant fevers ; he demon- 
strated that, in certain dyscrasic states, albuminuria being present, the renal 
apparatus becomes secondarily involved, the symptoms taking thereafter the 
appearance of true renal disease. 

All these constitute so many applications of chemistry to the study of the 
pathology and diagnosis of disease. 

He was, in a word, one of the founders of the application of biological chem- 
istry to the study of clinical medicine, both by his own works and by the 
direction he gave to the researches of his pupils. 

His works on medicine and therapeutics are of still more importance. 

He published researches on the hepatic lesions observed in the syphilis of 
the newly -born child ; on the pathogenetic and clinical distinction between 
jaundice due to hepatic derangement and that due to a dyscrasic state of the 
blood ; also an important work on the forms of paralysis consecutive to acute 
diseases; the discovery of the cause of incomplete hemiplegia, the face being 
affected on one side, the limbs on the other (cross hemiplegia, paralysies 
alternes) — an advance towards the doctrines of cerebral localization on which 
Charcot has shed such lustre ; also memoirs on the distinction to be estab- 
lished between diphtheritic and herpetic sore throat : and on internal erysip- 
elas, laying down the general law of the simultaneous development of the 
inflammation on the cutaneous and mucous surfaces. 

After freeing therapeutics from dogmatic prejudices and empiricism, Gubler 
bringing into play his universal erudition, soon placed himself among the 
authorities on the subject. He brought into common use, through his recom- 
mendations, aconitia, bromide of potassium, Calabar bean, chloral, eucalyptus, 
bromhydrate of quinine, and particularly jaborandi. 

After the Franco-German war, he took up the study of the mineral springs 
of Europe, and, although rendering justice to those beyond the Rhine, he 
demonstrated that none of them were superior to the waters of the Pyrenees, 
the arsenical waters of Manif'and of Mont-Dore and others. 

In his private character he was universally beloved. Many a needy student 
he aided by advice and pecuniary advance. He spent each year a large sum 
among his patients at Beaujon Hospital, and he made a donation for the per- 
manent support of a bed. 

He loved young people, encouraging their efforts and not seeking to repress 
the ardor of imagination. He received them with large hospitality at his 



PROF. ADOLPHE GUBLER. V 

house, rendered more pleasant by the presence of his amiable wife, a daughter 
of the sculptor, David D' Angers. 

Like his predecessor, Trousseau, he succumbed to a chronic affection of the 
stomach, but he continually put off the period of repose rendered necessary by 
his declining health. 

Towards the close of 1878, he was president of the board convened for the 
Concours of Internes. The subject given was albuminuria. The writer was 
present at the earlier readings, and almost every candidate referred to the 
researches of Gubler. He must have felt flattered, for the subject to be treated 
at the Concours is drawn by lot and the candidates locked up, so they have 
nothing but the memory to draw upon. He must have then remarked the 
wide-spread influence of his teachings. But before the Concours was finished 
he was obliged to give up, and retired to his villa, near Toulon, where he 
expired April 20th, 1879, in his fifty-eighth year. 

A few words from his own writings will best characterize his method : " For 
those who cultivate the science of man there are two principal methods of 
seeking the truth. While some, taking a side-path leading to rapid results, 
seek through experimentation on animals to establish the fundamental laws 
of vital organization, in order to make applications of them to the human 
species, others interrogate man himself to obtain the information he alone is 
capable of giving, and attempt, by patient and laborious observation, to dis- 
tinguish among the phenomena common to man with all living beings those 
peculiarities of organization and function proper to him alone. 

" The first are known as experimental physiologists ; the latter are simply 
physicians. 

"All contribute equally to the advancement of biological knowledge, each 
one in the measure of his own personal capacity ; and absolute pre-eminence 
cannot be attributed to either of the methods into which is subdivided the 
great and essentially modern scientific method." 



TABLE OF CONTENTS. 



PAGE. 

PREFATORY NOTE 3 

BIOGRAPHICAL SKETCH OF PROFESSOR GUBLER 5 

TABLE OF CONTENTS 11 

CHAPTER L— GENERAL THERAPEUTICS 17 

General Therapeutics : Therapeutics first commenced by empiri- 
cism — Difference between a remedy and a medicament. Remedies : 
Moral — Love, victory, music, reading, travels, amulets, homoeo- 
pathy ; Ponderable — Mechanical apparatus, percussion ; Biological 
— Globules of the blood, virus, hybridity, ethnics. Medicaments : 
Attempts at classification — Dangers attending all classifications. 
Physiological Properties : Mechanical Action — Mercury, oil of 
sweet almonds, mucilages, charcoal, tannin, ammonia, iodine, and 
bromide of potassium ; Chemical Action — Old theory, effect through 
presence, alkalinity, acescence ; Histological Combination — Its laws ; 
Dynamic Action — Applications of the theory of the correlation of 
forces. 

CHAPTER IL— GENERAL THERAPEUTICS— [Continued] 30 

Specifics in Therapeutics : The doctrine of signs ; Dynamizing 
Action — Alkaloids, glucosides, tea, coffee, coca, mate. Criticism 
of the Expression " Tissue-saving medicaments," or agents lim- 
iting waste. Theory of Organic Forces : Examples ; Adynam- 
izing Actions — Tonics, stimulants, radical forces, and acting forces. 
Effects of Medicaments: Physical, chemical and organic — 
Preponderance of the organism in the effects of medicaments — 
Positive and negative — direct and indirect, transitory and durable 
effects, (alteratives) — Arsenic. 

CHAPTER III. -GENERAL THERAPEUTICS— [Continued] 42 

Correlation of Organic Forces — The organism makes use only of the 
natural forces — Application to the action of electricity — All medi- 
cinal action reduces itself to an exchange of matter or of force — 



12 TABLE OF CONTENTS. 

Importance of the organic substratum — Ergotine and strychnine — 
Cause of the election of organs by medicaments ; Physico- Chemical 
Constitution — Phosphorus, phosphates of the alkaline earths, arsen- 
iate of lime, iron, salts of potash, introduction of medicaments, 
alcohol ; Affinity of the Histological Elements — Alcohol, ether, 
lecithin, protagon, myeline, cerebric acid, alkaloids — Physical 
reason for those affinities — Dyeing by coloring substances ; Differ- 
ences in Organic Sensibility — Extensor and flexor muscles ; Means 
of Elimination of Medicaments. Mineral Substances : Chemical 
composition; Perfect — Sulphate of soda; Imperfect — Oxalates, 
cyanides, chlorates, chlorides, iodides, bromides, arseniates, salts 
of iron, salts, of copper; Ill-defined Combinations; Unstable Combi- 
nations — Hyposulphites, hypochlorites. 

CHAPTEK IV.— GENEEAL THEEAPEUTICS— [Continued.] 55 

Organic Substances : Simplicity of composition ; Nature of Elements 
— Anaesthetics, hydrocarbons; The Part of Nitrogen; Molecular 
Grouping — Starch, gum, dextrine, vegetable and animal glycose, 
glycocol, benzoic acid, nitrous ether, nitrite of ethyl, cacodylic 
acid ; Chemical Composition — Curara and strychnine, apomorphine ; 
Conveyance of Medicamental Action — Inhibition, capillarity, conta- 
gion, reflex action, liquefaction. 

CHAPTEK V. — AVENUES FOE THE INTEODUCTION OF 
MEDICAMENTS 67 

Solvent Action op Albumen : The Part of Gravity in Absorption — 
Gingival deposits, tattooing. Avenues for Introducing Med- 
icaments: Digestive Tract; Stomach — Inconveniences of this 
method — Decomposition of medicaments in the stomach. 

CHAPTEE VI. — AVENUES FOE THE INTEODUCTION OF 
MEDICAMENTS— [Continued] 77 



The Stomach [continued'] — Intolerance, trismus, cancer ; Lesser 

Methods to retain its functions of absorption — Enveloping with fat 
and with gelatine — Advantages of absorption in the intestinal tract ; 
Larger Intestine — Its advantages, its facilities — Medicinal injec- 
tions — Local action — Echoes of sensibility. 

CHAPTEE VII. — AVENUES FOE THE INTEODUCTION OF 
MEDICAMENTS— [Continued] 88 

Madder — Weakness of absorbing faculty, except in pathological cases ; 
Urethra — The same ; Preputial Mucous Membrane — Some local ad- 



TABLE OF CONTEXTS. 13 

vantages; Vaginal Mucous Membrane — The same; Uterine Mucous 
Membrane — Dangers of this avenue — Uterine injections; Ocular 
Apparatus — Colly ri urns; Nasal Fossa and Pharynx; Eustachian 
Tube, Tympanic Cavity; Respiratory Organs — Gases and vapors, 
turpentine, sulphuretted hydrogen; Liquid Bodies — Kapidity of 
their absorption ; Solid Bodies ; Pulverulent Solid Bodies; Fumiga- 
tions; Inhalations. 

CHAPTER VIII.— RESPIRATORY METHOD ; INHALATIONS ; 
FUMIGATIONS 99 

Fumigations — Their origin — Olfactory inhalations — The part which 
water performs in fumigations — Emollient inhalations — Inhala- 
tions of mineral waters, sulphurous inhalations — The sulphurarise ; 
Inhalations of Dry Vapors— Camphor, tar, essence of turpentine — 
Eucalyptus, datura and belladonna cigarettes — Nitre-paper cigar- 
ettes — Inhalation of opium ; Inhalations of Carbonic Acid, of nitro- 
gen, of compressed air, of oxygen. 

CHAPTER IX. — AEROTHERAPY; ATOMIZATION OF LI- 
QUIDS 109 

Compressed Air — Its effect — Asthma; Barified Air — Anaemia at high 
altitudes; Inhalations of Oxygen — Accumulation of oxygen in the 
blood ; Ozone ; On the Atomization of Liquids — Experiments. 

CHAPTER X.— ATOMIZATION OF LIQUIDS 120 

Chemical Alterations of Atomized Mineral Waters ; Physiological Action of 
Atomized Douches — Percussion, temperature, chemical composition, 
precautions to be taken — Pulmonary atomizing of sulphate of qui- 
nine solutions ; Atomization in Ocular and Uterine Cases ; Aqua- 
puncture. 

CHAPTER XL— OPEN WOUNDS; CUTANEOUS METHODS 12S 

Absorption through Wounds; Absorption by the Serous Cavities; Cutaneous 
Absorption — Fallacy of the arguments advanced in favor of absorp- 
tion through the unimpaired skin — Refutation of those arguments. 

CHAPTER XII.— CUTANEOUS METHOD; BATHS 140 

Cutaneous Absorption [continued'] : Action of fatty bodies — Volatile 
substances — Action of the law of gaseous diffusion — Processes 
adapted to favoring absorption through the skin — Specialty of 
certain regions — Medicinal baths, their value. 



14 TABLE OF CONTENTS. 

CHAPTER XIII. — DIADERMIC METHOD; HYPODERMIC 
METHOD -. 150 

Diadermic Method — History — Mayer's hammer — Ammoniacal blister — 
Precautions to be taken — Its advantages and disadvantages ; Euto- 
dermic Method — History — The life-awakener ; Hypodermic Method 
— History. 

CHAPTER XIV.— HYPODERMIC INJECTIONS... 160 

History [continued] — Substances that can be injected; Injection Syringes; 

Alkaloids and Glycosides — Curara — Mineral salts — Nutrient substances — 
Serum in the blood — Peptones ; Physical Requirements for Injections 
— Solubility — Water — Alcohol — Glycerine ; Chemical Requirements 
for Injections — Effects of acids — Greater solubility of salts — Excep- 
tions ; Effects of Alkalies — Correctives —Albumen — Hydrobromic 
acid ; Standards of Solutions. 

CHAPTER XV.— HYPODERMIC INJECTIONS— [Continued] 170 

On the Choice of a Region — Tolerance of certain regions — Facility for 
absorption ; Injection loco dolenti — Special regions ; Manner of Ope- 
rating ; Solution — Its standard — Its concentration — Algae — Their 
effect ; Preventive Methods against the Development of Algce ; Local 
Effects of Injections. 

CHAPTER XVL— HYPODERMIC INJECTIONS— [Continued].... 182 

Common Local Phenomena — Local phenomena which vary with the sub- 
stances injected ; Diffused General Phenomena — Injections of water 
— Phenomena of imbibition, of sympathy, of contiguity, and of 
continuity; Rapidity of Action of Hypodermic Injections —Their con- 
stancy of action. 

CHAPTER XVII.— HYPODERMIC METHOD -[Continued] 194 

Proportional effect of the different substances through the stomach and by 
the hypodermic way — Causes of this difference — Local accidents 
attending hypodermic injections — General accidents. 

CHAPTER XVIII.— HYPODERMIC METHOD— [Concluded] ; 
ACUPUNCTURE ; TRANSFUSION 205 

Substances for which the hypodermic method is unfitted. — Objections 
to the method ; its advantages preponderate — Acupuncture, electro- 
puncture, parenchymatous, or substitutive method of injections — 
Introduction of medicaments through the vascular system — History 
of transfusion — Principles. 



TABLE OF CONTENTS. 15 

CHAPTER* XIX.— TRANSFUSION OF BLOOD— [Continued] 215 

Different methods of transfusion — Apparatus — Expected effects of 
injected blood — On the selection of blood, whether arterial or 
venous, animal or human. 

CHAPTER XX.— TRANSFUSION OF BLOOD— [Continued] 226 

Quantity of blood to be introduced — Manner of operating — Who should 
supply the blood — Venous transfusion — Mediate and immediate 
effects of transfusion — Indications and counter-indications. 

CHAPTER XXI.— INJECTIONS INTO THE BLOOD; TRANS- 
FORMATIONS UNDERGONE BY MEDICAMENTS 238 

Medicinal infusions into the blood — Intravenous injections. Trans- 
formations Undergone by Medicaments in the Organism : 
Immediate Changes — Nitrate of silver ; Changes in the Primce Via — 
Temperature — Cold drinks — Negative functions of the mouth — 
Active functions of the stomach ; Modifications in the Intestine — 
Functions of fatty bodies, and of albuminous matters — Gas. 

CHAPTER XXIL— ALBUMEN AND THE ALKALINE CHLO- 
RIDES; ARSENIC 251 

Albumen and the alkaline chlorides — Role of albumen in the economy 
— absence of certain chemical phenomena in the human organism 
Arsenic. 

CHAPTER XXIIL— ARSENIC— [Continued] 289 

Its passage through the system — Role of the liver — Plasma — Histologi- 
cal elements — Topography of arsenic in toxicology — Death by 



CHAPTER XXIV.— ARSENIC— [Continued] 301 

Albuminuria, its interpretation — Concerning death by arsenic [con- 
tinued] — Importance of taking into consideration the difference in 
doses — Modes of poisoning by arsenic. 

CHAPTER XXV.— ARSENIC— [Continued] 314 

Diagnosis of poisoning — Difficulties encountered — No pathognomonic 
symptoms — Medico-legal considerations — Imbibition by certain 
substances — Histologic deposits. 

CHAPTER XXVI.— ELIMINATION OF MEDICAMENTS 329 

Variable sojourn of different substances in the organism — Causes of 



16 TABLE OF CONTENTS. 

this variability — Variable rapidity of elimination — Choice of 
elimination made by medicaments. 

CHAPTEE XXVII.— ELIMINATION OF MEDICAMENTS— [Con- 
tinued] 341 

Influence of different doses— Practical applications — Under what form 
substances are eliminated, intact or more or less transformed. 

CHAPTER XXVIII. — ELIMINATION OF MEDICAMENTS— 

[Continued] 355 

Oxidations in the economy — Variations in the action of remedial agents 
— Role of medicaments — Role of the organism. 

CHAPTER XXIX.— ACCUMULATION OF REMEDIAL AGENTS, 369 

Insignificance of small doses — Therapeutic minimum — Tolerance and 
intolerance — State of the organs of absorption — Individual condi- 
tions — State of the secretions. 

CHAPTER XXX.— PREVENTION OF ACCUMULATION 382 

Means to avoid accumulation of doses — Administration in pill form 
condemned — Accumulation of action different from accumulation of 
doses — Causes and variations of accumulation of action. 

CHAPTER XXXI.— FORCE OF HABIT 395 

Force of habit — Frequent repetition — Influence of organic predisposi- 
tion, or of local organic condition. 

CHAPTER XXXIL— INTOLERANCE , 406 

Intolerance — Adjuvants — Synergetic and antagonistic substances — 
Counter-poisons and antidotes. 

CHAPTER XXXIIL— ANTAGONISM BETWEEN MORPHINE 
AND ATROPINE 417 

Therapeutic antagonism in general. 

CHAPTER XXXIV.— CONDITIONS AFFECTING MEDICINAL 
ACTION 426 

Influence of the size of the body ; of sex ; of age ; of temperament ; 
of manner of living ; of race ; of climate. 

INDEX 437 



The Principles and Methods 
of Therapeutics. 



CHAPTER I. 
General Therapeutics. 

General, Therapeutics : Therapeutics first commenced by empiricism 
Difference between a remedy and a medicament. 

Remedies : Moral — Love, victory, music, reading, travels, amulets, homoeo- 
pathy. 
Ponderable — Mechanical apparatus, percussion. 
Biological— Globules of the blood, virus, hybridity, ethnics. 

Medicaments: Attempt at classification by naturalists, chemists, therapeutists 
and physiologists. — Dangers attending all classifications. 

Physiological Properties: Mechanical Action — Mercury, oil of sweet 
almonds, mucilages, charcoal, tannin, ammonia, iodine, and bromide of 
potassium. 

Chemical Action — Old theory, effect through presence, alcalinity, acescence. 

Histological Combination — Its laws. 

Dynamic Action — Applications of the theory of the correlation of forces. 



Gentlemen : 

During a long series of ages those who practiced the art of 
healing, handled remedies in about the same fashion as children 
use gunpowder — aware of the marvelous or terrible effects of 
their weapons, but having no idea as to the nature of the force 
brought into action, its real power, the exact course of the pro- 

(17) 



18 PEINCIPLES AND METHODS OF THERAPEUTICS. 

jectile, or its range. In other words, old-time physicians not 
having the necessary exact instruments for the rigorous evalua- 
tion of phenomena, and being deprived, moreover, of all means 
for experimental control, could but imperfectly realize the inten- 
sity of action of remedies and their operative mechanism ; they 
were unacquainted with the means of introduction and disper- 
sion of remedies, their organic relative affinities, the alterations 
they underwent through the system, and the paths followed by 
them in leaving it. In this first period of empiricism, therapeu- 
tics was indeed no more than the art of healing. 

After a time therapeutics became a real science, having its 
own principles, its methods, and its. processes of investigation — 
processes, method and principles which it holds in common 
with physiology, of which it is a dependency. Only since 
the knowledge we have obtained of organism and the modifi- 
cations it can be made to bear, can we make certain useful dis- 
tinctions. 

In the first place, we can distinguish a remedy from a medica- 
ment. Remedies and medicaments are not to be confounded ; 
the term remedy may be applied to everything that cm be made 
use of in healing. You will in due time see that the agents that 
can be thus used are in great variety ; on the other hand, medica- 
ments are relatively limited. 

There are all sorts of means of curing. We have at our dis- 
posal moral, physical and material means ; among these there 
are those that are imponderable. Who among you is ignorant 
of the marvels of electricity? The other imponderable fluids 
are equally called upon to render real services to the art of 
healing. 

From ponderable substances we often expect the most varied 
results : you will find that there are some whose coarsest physi- 
cal properties are utilized, while from others we expect more 
intimate actions. 

A few words upon each of these great divisions among 
remedies. 

Let us first speak of the psycho-moral treatment. One must 



GENERAL THERAPEUTICS. 19 

know but little of life not to be aware of the influence which 
the moral has upon the physical. If Cabanis has been able to 
write a book upon the influence of the physical on the moral, a 
work of equal interest could be compiled on the influence which 
the moral lias on the physical. As a legendary example we 
have Erasistrates guessing that Stratonica was in love with An- 
tiochus Soter, and curing his patient by a marriage. Examples 
like these are not rare; you probably have met with them. 
They are not ahvays within the domain of science. You have 
but to read what all army physicians have written on the part 
which moral influence bears on the consequences of wounds. 
Whenever an army is victorious, wounds heal ; if it be defeated, 
they are aggravated. I have said enough to make you under- 
stand that influence. 

It is, therefore, indispensable to use such means as are capable 
of rousing the moral forces. These means you will employ not 
only against diseases, so called, of the mind, but against all others 
as well. We make use of moral means not only in cases of 
mental alienation and in exhaustion, but in diseases of long 
standing, among those affected with tubercles, with cancers, and 
with disorders of the heart. At times we appeal directly to the 
mind in order to rouse it; this is not the best method, I confess; 
it is even an ineligible one, especially where deep disorders of the 
mind are concerned. To one talking out of reason, it would 
seem natural for us to present him with a well-constructed syl- 
logism ; but this method in such a case is hardly ever success- 
ful. Better success is met with by acting indirectly upon the 
imagination ; as for example, when passion is appealed to 
through the medium of the stnses. You all know the influence 
of music, and the results obtained from it. Heading, relaxa- 
tion and especially changes. of air and place, presented to those 
whose minds are slightly affected, all these supply excellent 
means of improvement. 

In a word, there are innumerable circumstances in which you 
will be obliged to uphold the courage of patients suffering under 
long and almost always fatal diseases; in some cases you will 



20 PRINCIPLES AND METHODS OF THERAPEUTICS. 

even have to deceive them. It is under such conditions that 
certain means now out of use — and which I do not recommend 
— various superstitious practices in archaic medicine have been 
of use ; for example, amulets and incantations. 

At the present day we have them in infinitesimal doses ; 
homoeopathy is nothing else. You smile? I am able to tell 
you of a recent instance. Not long ago Dr. Potain and myself 
were called upon to attend a patient who thought himself suffer- 
ing from a disease but of a few days' standing. He was under the 
care of a celebrated homoeopath ist, who kept up his courage and 
dosed him with cold water. Up to that time the patient ex- 
perienced nothing more than slight fatigue; he was a great 
huntsman, but could no longer enjoy his pastime as was his 
wont ; all at once formidable symptoms develop ; he is taken 
with vomiting of blood. The homceopathist becomes fright- 
ened ; he did not believe the disease was so serious, but now con- 
cludes to call in physicians. That unfortunate patient had an 
organic disease of the heart which had not been detected. 

In conclusion, I may add that our pseudo-brother asked leave 
to return for the purpose of upholding the patient's courage. 
This, evidently, was the object he had in view ; there is nothing 
culpable about it, but a similar result may be obtained by other 
methods. I repeat it, it is proper to encourage a patient, to in- 
dulge him even with well-meaning falsehoods, for there never 
was a case to which some relief could not be brought, and that 
is what is expected of you ; the patient must have his illusions 
sustained, consoling words are to be spoken to him, according to 
the precept of Pindarus, who in his Pythics advises us " to 
charm suffering by kind and consoling words." 

The therapeutic agents supplied by imponderable forces are 
interesting. It is not customary to dedicate a chapter to thermo- 
therapeutics, yet valuable considerations might be pointed out 
in it. 

You all know the influence of heat in the recovery of strength 
and you are aware of the influence which light possesses. 

We are especially indebted to ponderable substances for the 



GENERAL THERAPEUTICS. 21 

greatest services. They supply the arsenal of therapeutics, but 
they are used for different objects. 

At times we look to them for their coarsest physical proper- 
ties, as in external therapeutics. 

It is here we place hydro-therapeutics both hot and cold, for 
douches do not only operate by heat and cold, and the re-actions 
which follow ; they also exert a mechanical action, percussion. 

But oftener ponderable substances are looked to for intimate 
molecular operations which take place in the very structure of 
our tissues, operations upon which we shall have more to say 
hereafter. These are the real pharmaceutical methods, the real 
medicaments ; consequently they are the methods in the art of 
healing upon which I shall dwell. 

Finally recourse is sometimes had to ponderable substances 
which not only possess the properties of matter, but are more- 
over endowed 'with those of organized beings, real organisms. 

When I say that the vital properties of a certain number of 
bodies are made use of, I have reference to the blood globules. 
Introducing blood into an anaemic person cannot be called giving 
him a medicament. 

The same may be said when we introduce a virus which has 
no typical form, but which nevertheless possesses a certain num- 
ber of properties belonging to organized living bodies, and 
which behaves like a collection of organisms properly so-called. 
Vaccine virus is a remedy but not a medicament. 

An interesting chapter in therapeutics is that which aims 
not at individuals, but at races. It contains the modifica- 
tions we produce in organisms, by means of a cross estab- 
lished between individuals of the same species, endowed with 
opposite diathetic qualities and temperaments ; or else be- 
tween different species (I give to species the meaning of species, 
eedo<;. I admit a single human genus, but different species, 
formed by more or less deep modifications, acquired in course of 
time by subjects which have lived under special conditions.) 
Well, I say that by crossings, we can advantageously modify 
morbid dispositions. For example, if it were true that the 



22 PRINCIPLES AND METHODS OF THERAPEUTICS. 

negro race is exempt from carcinoma, would there not be an 
advantage, (I do not speak for the white race; it is always un- 
pleasant to tint one's self,) but for the Hindoos to cross themselves 
with those superb races met with in certain parts of Africa, and 
thus place themselves beyond the reach of cancer ? In short, 
whatever that idea may be worth, I assure you that in the cross- 
ing of lymphatic and bilious subjects, there are developed con- 
ditions for the disappearance of a certain number of diathetic 
diseases which are a plague upon some populations. I believe, 
for example, that if the Russians, with whom scrofula is so 
prevalent that they readily tell you, " Doctor, in my family we 
are all scrofulous," were to cross themselves with the Spaniards, 
the consequence would be a decrease of scrofula. 

There are, therefore, a great number of remedies which are 
not medicaments. Medicaments, although forming but a frac- 
tional part of remedies, are nevertheless the most important por- 
tion of our therapeutic arsenal. They are innumerable, hence 
difficult to classify. 

Many classifications have been attempted, resting upon differ- 
ent bases ; at one time attention was given to the organoleptic 
properties ; this was clearly a primitive classification ; again an 
attempt was made to classify according to natural orders. 
Naturalists and botanists have favored this idea, which may be 
useful, since Linnaeus has taught us a great truth by showing 
that substances which approach one another in their natural 
characteristics are in general very analogous, not to say similar as 
to their properties. But exceptions to this rule are so numerous 
that his classification could not stand against them. A classifi- 
cation according to chemical composition was also attempted; 
this proved to be no better, because enormous disparities exist 
between substances which resemble one another in their physio- 
logical action. Finally classifications have been made based 
upon therapeutic effects. We have all been tempted to make 
our own. For my part I have never had the pretension of mak- 
ing a therapeutic classification, but I have attempted one based 
upon physiological effects. 



GENERAL THERAPEUTICS. 23 

I hasten to admit that it is not any better than the others, and 
I add that an irreproachable natural classifiation, that is, one not 
fettered by system, is absolutely impossible. Without indulging 
in many details, I will explain the reason why. 

The same substance, according to the constitution of the sub- 
ject, according to conditions peculiar to the substance itself, may 
produce not only entirely different, but inverse effects. You 
may then understand how difficult it is to base our views upon 
the properties of a substance in order to classify it under any one 
head within the limits we may wish to establish, since other rea- 
sons may entitle it to an entirely opposite place. 

I have now reached a very important question, and one that 
should be settled at the beginning of all explanations of thera- 
peutics, considered in a general way. That question is the mode 
of action of the various substances employed as medicaments, and 
the different effects which these substances are called upon to 
produce. 

In a number of works attempts have already been made to 
understand this intimate mechanism; but never in an abstract 
way has the inquiry been made as to the effects produced by 
medicaments upon living beings. We have to consider three 
kinds of actions — these are : mechanical and chemical actions, 
and those connected with molecular physics, which I ask your 
permission to call by the name of dynamic. 

Mechanical Actions. — It seems at first strange that such actions 
should be attributed to medicaments. You will see, however, 
that a certain number of examples present themselves. 

For instance, pure metallic mercury has been introduced into 
the intestine to resolve a volvulus: it acts by its weight in 
unfolding the intestine. 

Oil of sweet almonds given as a laxative, is simply a method 
of facilitating the passage of the excrements through the intes- 
tines ; it does not act as a substance capable of inducing a 
secretion. 

For a similar purpose are certain mucilaginous substances 
taken as a drink. Thus you will find, especially in popular 



24 PRINCIPLES AND METHODS OF THERAPEUTICS. 

practice, many persons who drench themselves with a more or 
less viscous solution, obtained by boiling flaxseed. This is a 
good way to facilitate the exoneration of the intestine. 

Here are other facts : A peripheric excitation may be obtained 
by purely mechanical means. (I will not mention those that are 
simply remedies.) 

At times it may be substances provided with very sharp- 
pointed and stiff hairs, which, penetrating through the epidermis 
to the dermis, produce an itching sensation by mechanical ex- 
citement, and consequently all the phenomena of cutaneous irri- 
tation or awakening of sensibility, as well as those of revul- 
sion, as it is obtained by energetic methods. 

I shall say nothing about nettles, of which my teacher, Trous- 
seau, and myself have made such frequent use, for the hair in 
nettles is imbedded in a gland which contains chemical substances 
that cannot be included in the study of mechanical actions 

Powdered char coal administered in quite a number of dys- 
peptic conditions, especially as an absorbent of gases, only acts 
as a mechanical agent, and yet it has been observed that this 
charcoal powder produces very remarkable exonerating effects. 
Other substances facilitate or impede the flow of liquids in the 
capillary tubes. Thus tannin reduces the facility with which 
blood circulates through the capillaries. 

There are other substances which act in an inverse manner. 

Ammonia, which, when in solution in water, facilitates its in- 
troduction in the capillary tubes, acts in the same manner in the 
capillary vessels of living individuals. Similar effects are pro- 
duced by bromide and iodide of potassium which, in this re- 
spect, are absolute congenerates. 

There are, therefore, a certain number of instances in which 
medicaments produce real physical effects. But a medicameut 
generally operates through its chemical actions. 

Formerly, effects from mere presence would have been ad- 
mitted, but at this day, especially considering what we know of 
the laws of correlation of forces, such explanations can no 



GENERAL THERAPEUTICS. 25 

longer be allowed. Indeed, in order that a body should act, not 
only must it be present, it must be all the while yielding either 
force or substance. In the edition of 1846 of Trousseau's 
work, I myself held out the opinion that cyanhydric acid must 
act in the blood towards the globules by simply the fact of its 
presence; we now know that it acts by a perfect combination of 
haemoglobine, arresting its functions. I repeat it : action through 
presence alone, no longer exists j medicaments act by forming 
combinations ; these combinations are in great variety, and take 
place either with mineral organic substances, or even with the 
plasma or albuminoid principles of the blood, or finally, but 
at a later period, with the histological elements themselves. 

In this purely chemical manner of acting of substances, quite 
different categories are to be established. 

Carbonate of soda, or Vichy water, is introduced in the 
stomach for the purpose of neutralizing the acids which have 
formed there at the expense of the alimentary substances. That 
is the simple phenomenon as far as the action of the medica- 
ment is concerned, when the latter is considered as a chemical 
body ; but by the introduction of alkaline substances, there is 
produced an increase of causticity in a certain number of the 
fluids in the general economy, first of all in the blood. On the 
other hand, when it is desirable to increase the acid qualities of 
certain liquids, such, for instance, as sweat and urine, acids are 
introduced. Although more difficult to maintain, this condition 
is reached iu a certain number of cases. 

In other cases, to which I but just now alluded, substances 
introduced into the circulation must combine with the plasma 
of the blood, and then take part in the formation of the histo- 
logical elements. 

Just here two cases present themselves : At times there are 
normal substances in the organism, which become real elements 
of it: for example, the phosphates and carbonates of the earths, 
iron, cod-liver oil. Other substances behave in about the same 
way, in so far that, after having entered, they combine with the 
plasma, and take part in the formation of the tissues; but then 



26 PRINCIPLES AND METHODS OF THERAPEUTICS. 

these substances either exaggerate the proportions of normal sab- 
stances, or, if they are closely similar to the substances, they 
substitute themselves for them. Here are a few examples : 

You introduce a large quantity of sulphur into the economy ; it 
belongs to the same natural group as oxygen, and, as-such, will 
substitute itself for oxygen in the composition of the histological 
elements, and particularly in the nervous system. 

But we are here in presence of a normal substance, since sul- 
phur exists in the economy. Let us take a substance which does 
not occur in the organism: arsenic, for example. Well, it will 
behave like sulphur. It will substitute itself for a certain pro- 
portion of phosphorus, for the reason that arsenic and phosphorus 
are substances belonging to the same group. 

All this is not simply a vision of the mind. There are facts 
which, to me, seem to demonstrate the truth of this method of act- 
ing among a certain number of substances. Fifteen years ago, 
I attended a woman who had poisoned herself with arsenic. She 
had taken, so she said, a large teaspoonful of arsenious acid. 
Just think what a terrible quantity of poison that represents. 
After the choleriform accidents, she experienced febrile phe- 
nomena, and presented, finally, a paralytic state so very similar 
to saturnine paralysis, that Duchenne (of Boulogne) was deceived 
by it. But this is not, for the time being, the interesting part 
of this case. This woman was obliged to remain a very long 
time in the ward, suffering from multiform accidents. When 
she was admitted, some thirty days had elapsed since she had 
taken her poison, and her urine was laden with arsenic. Soon 
after, the elimination of arsenic stopped. I then gave her iodide 
of potassium, and under the influence of this treatment, the 
elimination of arsenic commenced anew. 

Here, however, is the really interesting point in the case. This 
woman had been admitted in the middle of the month of Octo- 
ber, 1864; on the 16th of May next following, I had her hair 
cut ; that hair contained an enormous proportion of arsenic — at 
the end of eight months. 

Now, you know what are the interpretations given to the 



GENERAL THERAPEUTICS. 27 

phenomena connected with the storing away of poisons. No 
very clear idea seemed to prevail as to how they could accumu- 
late ; it was said that poisonous substances, especially the metal- 
loids, were generally found in the parenchymas, especially in the 
hepatic parenchyma. But no one attempted to explain how, or 
why, this accumulation in reality takes place. It takes place in 
the histological elements themselves. 

Arsenic first locates in the plasma; it then forms a part of the 
histological elements. That is so true, that, at the expiration of 
eight months, the hair was full of it; now, it evidently could 
not have penetrated there except through nutrition. This is the 
only allowable interpretation that can be offered, as there is noth- 
ing in hair, except the cells, which, when united, form hair. 

Besides the manifestation of mechanical effects, of which we 
have given you some examples, besides the chemical effects which 
we have just recalled, medicamental substances, in their manner 
of acting, present phenomena which are connected with molec- 
ular physics. These are the effects which I propose to name 
dynamizing, and which remind us of what the imponderable 
fluids produce. 

You all know what, by general agreement, are called " endo- 
thermic" substances. They are compounds, in which heat, as 
we formerly expressed it — at the present day we should speak 
differently — is, as it were, imprisoned in a latent state. 

These bodies are very numerous, for we may say that latent 
heat is contained in all bodies; but there are a certain number 
which contain a great deal more than others. I need not insist 
upon it — you all know what a quantity of latent heat exists in 
water; you know the sum of the caloric which it gives up when 
it solidifies. Well, there are a great many bodies which likewise 
contain heat. 

I stated, awhile ago, that that expression was a good one before 
,,he doctrine of the correlation of forces was understood. At the 
present day, we would call them dynamized substances. In fact, 
those substances do not always yield up heat. Here, for exam- 
ple, we have a concentrated solution of sulphate of soda; it is 



28 PRINCIPLES AND METHODS OF THERAPEUTICS. 

saturated, and crystallization rapidly takes place. While it crys- 
tallizes, as in the case of water, there is a considerable elimination 
of heat ; in this instance, it is heat which is disengaged. 

Now, we take and dissolve arsenious acid : the solution is 
saturated. In the dark you will observe that phosphorescent 
rays are disengaged ; the phenomenon is of the same order as 
the one before mentioned, only, in the present case, it is under 
the form of light that part of the force is disengaged. 

A similar re-action takes place when arsenious acid passes from 
the vitreous to the opaque state ; that is, where, from amorphous, 
it becomes crystalline. 

Many instances thus occur in which heat, light and electricity 
are produced. These are well-known facts at the present day, 
and to dwell merely on those which particularly interest us, let 
me tell you that those mineral waters which rise from the bowels 
of the earth, possessed with a particular constitution, which has 
secured for them the name of " vitalized waters," carry with 
them to the surface, not only heat, but electricity ; so that, even 
by means of instruments of no great delicacy, the presence of 
both can be demonstrated, as has been shown long ago by Scout- 
etten. 

It thus becomes evident that those bodies which are endo- 
thermic, are, in reality, charged with forces, which they yield up 
under the form of heat, chemical action or light. 

You know what are " fulminates ;" that is, metallic nitrates : 
they are highly changeable combinations. 

It is because of the weak affinity which nitrogen has for the 
metals, that under the influence of the least shock those com- 
pounds detonate, and liberate forces of matchless potency 

There are, therefore, a great variety of forms under which 
force presents itself. Well, this force which I have just shown 
you as imprisoned in endothermic bodies exists in variable de- 
grees in what we call medicaments, particularly in the alkaloids, 
and in a certain number of neutral bodies. 

Only, herein lies the difference between fulminates, like dyna- 
mite, for instance, and the molecules of medicamental substances ; 



GENERAL THERAPEUTICS. 29 

that while these surrender their force slowly, steadily, and with- 
out shock, gun-cotton, and the nitrates yield up theirs in a vio- 
lent manner. 

In conclusion, while the substances of which we were just 
now speaking, may be considered as Leyden jars of excessive 
power, medicaments are, so to say, magnetic bars. But there 
always exists a surrender of force. And under the influence of 
this yielding up of force produced by the medicamental sub- 
stance introduced into the economy, structural modifications take 
place in our organs ; our tissues may be said to pass under real 
allotropic conditions ; that is to say, they are either charged, or 
again, more or less exhausted, reminding us, in the former case, 
of ozone (O 3 ) or in the latter simply, of ordinary oxygen repre- 
sented by O. 

What I say to you here is not merely a guess or theory; 
it is at this day a demonstrated fact. I stated, upon observing 
that sulphate of quinine, without undergoing transformation, 
had saved from certain death patients impregnated with marsh 
miasma, that it must have yielded up force, it must have passed 
into an allotropic condition. 

Mr. Guyochin, analyzing the alkaloid which was present in 
the urine after having passed through the organism, found that 
it was no longer quinine, but quinidine and quinicine; that is to 
say, quinine which had lost its force and was reduced to im- 
potency. 

Here is, therefore, an experimental proof in favor of the doc- 
trine which I have developed to you. 



30 PKINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER II. " 
General Therapeutics— [Continued.] 

Specifics in Therapeutics: The doctrine of signs — lungwort, carrots, 
albuminates. 
Dynamizing Action : Alkaloids, glucosides, tea, coffee, coca, mate\ 

Criticism of the Expression "Tissue-saving medicaments," or agents 
limiting waste. 

Theory of Organic Forces : Examples. 

Adynamizing Actions: Tonics, stimulants, radical forces, and acting forces. 
Variability of effects in tonics and stimulants, strychnine, morphine. 

Effects of Medicaments : Physical, chemical and organic. Preponderance 
of the organism in the effects of medicaments. Positive and negative, 
direct and indirect, transitory and durable effects, (alteratives). Arsenic. 



Gentlemen : 

I have told you that in medicaments we nave to study element- 
ary actions, independent of the effects produced by these actions. 

Formerly, matters were not so difficult ; medicaments were 
endowed with peculiar virtues, they were considered as specifics ; 
under these circumstances it was not difficult to understand their 
mode of action. It was supposed that nature had endowed cer- 
tain plants with properties which rendered them apt to directly 
battle against disease, as though a single combat had taken place 
between the disease and the remedy. 

A doctrine of signs had even been invented, according to which 
nature was supposed to have inscribed upon the different pro- 
ductions of the vegetable kingdom the various ailments for 
which the medicaments at our hands were suitable. 

Thus the spots in the pulmonary or lung-wort indicated the 
use to be made of that ulant in tubercular phthisis, because in 



GENERAL THERAPEUTICS. 31 

that disease the lungs are crammed with something that resem- 
bles these spots. In the same way carrots were indicated in 
cases of icterus. 

At that time it was not difficult to understand the mode of 
action of medicaments : they possessed properties. They cured 
proprio motu by something that could not be explained by the 
laws of matter. 

With us, we are made to pause, and obliged to master much 
more difficult details in order to understand the mechanism of 
therapeutic agents. 

I have shown you that even in medicaments, that is, in sub- 
stances which we administer, there are mechanical actions ; and 
I have given you examples of these. But chemical actions are 
the most numerous; at times it is a simple chemical combination 
with the bodies existing in the organism, as when we free the. 
stomach from acids by the use of alkalies; again the combina- 
tions are with the tissues themselves, as when we produce, for 
example, cauterization. 

Finally, in other instances, the combinations are of a some- 
what peculiar nature; they no longer are the definite combi- 
nations with which you are acquainted, but combinations of the 
kind designated by the name of albuminates. 

You are aware that a great number of substances are con- 
sidered as entering into combination with albnminoidal matters; 
well, analogous combinations take place between the albumi- 
noidal matters in the body and medicamcntal substances. At a 
later period those substances go towards forming a part of the 
tissues; either, if normal, they become simple elements, or, if 
they are simply analogous to the normal substances, they enter 
and substitute themselves for these substances. 

These are the different kinds of chemical actions which can be 
produced by medicaments. When we last parted we were con- 
sidering dynamizing actions. I desire to add this much, that by 
means of those substances which are capable of yielding up 
forcej we succeed in dispensing the organs from the necessity of 
producing it. 



32 PRINCIPLES AND METHODS OF THERAPEUTICS. 

The organs, as you know, produce force. Take for instance 
the muscle, the physiology of which is well known. It is 
obliged to burn not perhaps its own substance, but the residuum 
of denutrition, and it does so to produce force. If it does not 
do this, it lacks the necessary force to contract itself. Now, en- 
dothermic substances are capable of supplying to the muscles 
and to the nervous system the force which they would be obliged 
to produce in order to act. 

This opinion seems to me, and I tell you so in advance, ap- 
plicable to a great number of medicinal substances. For ex- 
ample, the alkaloids, and the analogous principles which are 
neutral bodies, glycosides, those substances endowed with such 
immense power, that in almost infinitesimal doses they produce 
enormous effects (J of a milligramme, as in the case of aconite), 
seem to me especially to possess this dynamic action ; that is, 
they seem, in the selection they make of certain parts, to be 
specially capable of supplying strength and of exciting the ner- 
vous system. 

At any rate, this seems demonstrated, as far as a certain num- 
ber of principles are concerned, which belong as much to hy- 
giene as to therapeutics. I have reference to those principles 
which exist in tea, coffee, coca, mate, etc. These substances, at 
present, are admitted by a certain number of physiologists, 
among the substances which are capable of supplying strength. 

A French agriculturist, Count Agenor de Gasparin, some 
thirty years ago, called attention to the singular property possessed 
by coffee, the best known of those substances in France and 
Belgium, of sustaining strength, while it contributed but very 
little ponderable substance. He pointed out that the laborers 
working in the coal mines of the Ardennes, ate but little, but 
with coffee were able to produce enough strength for their work 
in the mines. This disagreement between the small quantity of 
substance introduced for consumption, and the amount of force 
produced has called attention to new properties which were but 
little thought of. But there was difficulty as to the interpreta- 
tion. For a number of years certain expressions, which I ^con- 



GENERAL THERAPEUTICS. 33 

sider absolutely defective, have crept into scientific language ; 
these wordings claimed to express the manner in which the above 
phenomena took place. Thus such substances have been desig- 
nated by the name of " tissue-saving foods," or by the univocal 
expression of " anti-deperditeurs " (anti-deperditives). This is 
not new, although it was offered as such at a certain period, 
during which it was considered as a sort of revelation, 

These denominations originated in the manner of understand- 
ing certain physiological and physio-pathological phenomena, the 
study of which already dates back over fifty years. W. Bocker 
was the first to observe that in our therapeutic arsenal there are 
a certain number of substances capable of arresting the move- 
ment of disassimilation as well as that of assimilation. 

In his opinion and that of his followers, they are substances 
capable of preventing organic denutrition. I believe myself 
able to show to you, that this method of speaking is as defective 
as is erroneous the idea upon which it rests. 

We shall see that to spare our organs by this process, to save 
ourselves from the need of increasing our resources by another 
alimentation, this is not properly the way to save. As to 
" anti-deperditives," it is again a still worse denomination, be- 
cause it would seem as if they were satisfied with the word, and 
believed that after saying alcohol is an anti-deperditive, they had 
unfolded a whole doctrine. I shall render palpable to you all 
that this method of comprehending the phenomenon is absurd. 
And this opinion, which I was first to express, has finally been 
adopted by a certain number of right-minded persons. 

Nothing is easier than to diminish the organic waste, and con- 
sequently to slacken the denutritive movement of the organs. 
We have only to suppress all excitants, intellectual excitants 
among others ; we can place ourselves in darkness, make use of 
stupefying agents ; by such methods we can diminish losses ; is 
it a way, however, of acquiring strength ? No ; it is only the 
way not to expend any. But, as it is only by means of respi- 
ratory combustion that we arrive at producing the strength 
necessary to our activity, it is evident that those who would sub- 

C 



34 PRINCIPLES AND METHODS OF THERAPEUTICS. 

mit themselves to this anti-deperditive regimen, would sink to 
the condition of certain nervous women in the Salpetriere. 
They drop into a species of imbecility attended by torpor, and 
become motionless, like Hindu bonzes. 

From this you understand that it is impossible to attribute 
the name of anti-deperdition to such marked effects as those from 
coca, which enables Indians to travel a long distance, relying 
only upon a small quantity of this substance ; or to those of cof- 
fee, which allow us, when occasion requires, to make use of great 
cerebral activity, without taking any more food than at ordinary 
times. This stimulating action in substances like tea, coffee and 
coca, can only be accounted for by a contribution of strength ; 
for this reason I have called these substances dynamizers or 
dynamophores, if you prefer it, the former word being already 
used in another sense. 

The question is to know what sort of force these substances 
supply us with. They furnish us with no other forces than 
those of the chemical substances themselves, be they organic or 
mineral. Only, we must here introduce a new idea ; it is that of 
the correlation of the physico-chemical and organic forces ; 
and I shall ask your permission to develop somewhat this view, 
because were I not to do so, I might be taxed with wishing to 
place life in an equation with heat. 

That is, however, what has been done in a certain number of 
documents, in which it was repeated that when I spoke of the 
correlation of physical and organic forces, I meant to say that 
with the aid of the physical forces, life could be engendered. I 
do not believe this : it is not in this way that I understand ths 
question. As scientists, we must acknowledge that in living 
beings, independently from all organization, there are forces 
which belong to brute matter. But there is something which is 
absolutely irreducible, it is formation, nutrition, that force which 
the ancients designated under the name of vis formativa, and to 
which the most ancient philosophers gave the name of evopjuov, 
the force which causes the organs to develop, and which enables 
the eye of the salamander to reproduce itself. That force, how- 



GENERAL THERAPEUTICS. 35 

ever much I seek, I can find no way by which to reduce to 
chemical combinations, or to the action of imponderables. In 
living beings what is absolutely individual to them is reproduc- 
tion and nutrition, which are one and the same. 

As Aristotle had said, as Lallemand (of Montpellier) has at a 
later date demonstrated, to the foregoing something still more 
irreducible must be added ; that is, thought. There, again, as a 
scientist, I am at a loss to understand, and I turn from that field 
which is of such difficult approach. But I claim that there, as 
well as in nutrition, in the genesis and repairing of the organs, 
qualities, and faculties are found, which belong solely to the 
living beings of all kingdoms, and that those faculties are abso- 
lutely irreducible to the action of inanimate matter. Hence it 
is not of these I shall speak ; but there are other faculties which 
belong to certain forms, to certain structures of organized matter, 
which are not irreducible to the laws of physics. Such are, for 
example, the muscular and nervous forces, myotility and neurility, 
names coined by Charles Robin, and that property possessed by 
the globules of the blood of taking up oxygen for the purpose 
of yielding it again. 

Those properties are not essential to living beings in general ; 
they are met with in certain beings, but are not everywhere 
found. They are not, consequently, indispensable to life ; they 
are, on the contrary, attached to a particular structure, and so 
long as this last exists, these properties are not found wanting. 
So long as the structural properties exist, the qualities, the func- 
tions of that structure persist. I have had, in former times, un- 
questionable examples of this, which it gives me pleasure to 
recall. On one occasion, at the Necker hospital, I had to com- 
plete the amputation of a limb which had been crushed. I sepa- 
rated the arm from its attachments. I was then tempted to ex- 
amine what was going on in the biceps, which, although stricken 
by death, had preserved its warmth. Out of the muscle I 
carved cubes, and I endeavored to produce a contraction in 
them. Nothing was easier, and by the most varied processes : 
by blowing upon them, by pricking them with a scalpel, by the 



36 PRINCIPLES AND METHODS OF THERAPEUTICS. 

use of a battery formed by a silver and copper coin. After a 
time the contractions would cease. I would take up another, 
and commenced anew. I then returned to the first, and again 
obtained results. This lasted during three-quarters of an hour. 
It proves to you that, even when deprived of life, this substance 
was still apt to perform its functions ; that is, force could trans- 
form itself into action, and consequently into mechanical con- 
traction. But, as I have observed, this force would become ex- 
hausted, and it was necessary to give the cubes rest before obtain- 
ing another series of contractions. This is quite analogous with 
what exists even among mineral substances which owe to their 
structure qualities that are not inherent in their chemical com- 
position. Take globules from an animal, they are quite different 
from those in man ; but, provided they are not any larger, they 
will behave, in the human circulation, in exactly the same man- 
ner as the blood globules of man ; and these globules preserve 
the property of favoring the exchange between oxygen and car- 
bonic acid during all the time that their existence lasts under a 
certain particular form which constitutes a structural condition 
analogous with that of crystal lizable mineral substances. 

Well, those organs which have particular properties attached 
to their structure, can be charged by substances such as the ali- 
ments, foods or medicaments I mentioned a while ago, in the 
same way as they can be charged by the aid of electricity. 

Let me, in a few words, tell you of one instance which can be 
classed under this head, and which is likely to convince you. I 
once had under my care at Beaujon, a patient who had taken a 
sudden cold, from which paralysis of the left arm had resulted. 
He was admitted quite shortly after the accident, and when I 
was called upon to examine him, I found that not only had he 
lost all voluntary movement in the upper left limb, and in that 
only, but also that electrical irritability was nearly all gone ; I 
could barely cause the biceps to harden a little. Under such 
conditions, as loss of voluntary movement and almost total ex- 
tinction of electrical irritability, it occurred to me to say to him, 
while the current was passing : " Why don't you carry your 



GENERAL THERAPEUTICS. 37 

hand to your chin." He replied, laughing : " You know full 
well I cannot do so." He was resisting. Finally he did as I 
asked him. I got him to renew the movement as often as I 
pleased ; all that was necessary was to allow the current to con- 
tinue. 

While he was performing that movement, I withdrew one of 
the rheophores ; his arm fell back, inert. 

What was taking place ? Matters were only a day or two old. 
Evidently the muscle had suffered no alteration ; only it was no 
longer producing force, it was incapable of causing a contraction. 
It possessed structure; I gave it force again by means of elec- 
tricity. These facts are far from being as singular, or as strange, 
as they appear at first sight. 

It is not very rare to observe, during the progress of certain 
diseases, cases of paralysis happening, in which the will loses its 
efficiency, and inductive currents become useless, but where the 
combination of these two agents, current and will, determine 
motion. 

Thus, I have often observed, and especially on one occasion, 
in company with Dr. Bounefin, cases of complete facial paralysis 
attended with impossibility of winking the eye. But during the 
passage of a continuous current — it is the best in such a case — 
the patient could close his eye. 

When he tried to close it without that, he could not. The 
current charged the muscle, and the will interposed to have the 
movement executed. 

These phenomena which I point out to you, that is, the return 
of force, and the calling into action of that force, under the influ- 
ence of the will, these are facts which, to my mind, leave but 
little room for doubt, and which demonstrate that either by the 
aid of substances charged with great energy, such as alkaloids, or 
by means of other substances which are as much within the 
province of therapeutics as of hygiene, we succeed in communi- 
cating force to organs which no longer produce any. 

But it is especially the imponderable fluids, such as electricity, 



38 PRINCIPLES AND METHODS OF THERAPEUTICS. 

which manifest, in the highest degree, this power of imparting 
force to those organs which stand in need of it. 

If almost all substances contribute force, there are some, never- 
theless, which seem to withdraw it. In the exchanges which are 
made, there is, at times, a loss. 

A while ago I spoke of imponderable fluids bearing force; 
heat will also bring some, but it must be, so to say, positive heat, 
that whose intensity is greater than the heat of our organs. On 
the contrary, if we have to deal with a temperature indicated by 
the sign minus ( — ), it is evident it will rob us of force. 

Now is the time to have you grasp the distinction which is to 
be established between tonics and stimulants. You will find that 
here there is confusion on all sides. You will be told alcohol is 
a tonic and a stimulant, two words that are actually in conflict. 

In speaking to you of those substances which contribute force, 
I have given you the true theory of tonics. We are to consider 
as tonics, those substances which are capable of increasing the 
" radical " forces, (to distinguish them from acting forces,) as the 
ancients called them. This distinction between radical and act- 
ing forces is an absolutely just one, and it should be retained 

Stimulants call organic activity into play. Every living organ 
is endowed with excitability ; that is its most general property. 
Anything can be a cause of excitement for most tissues; and 
stimulants are nothing more. You see that this is a great way 
from increasing the supply of forces. 

While tonics are means by which we enrich ourselves, stimu- 
lants are, in reality, means of impoverishment. I hasten to add 
that, in other ways, tonics and stimulants produce analogous 
effects. 

Take, for instance, strychnine : when but very little is used, 
the excito-motive power is increased. Give it, for example, to a 
paralytic patient, you supply him with the means of raising his 
body, when, otherwise, he could not do so; he can produce a 
greater number of efforts. But if you go beyond the due meas- 
ure — if, rather, too heavy doses are given — it is no longer an 
increase of radical force that is produced, but a real excitement. 



GENERAL THERAPEUTICS. 39 

Likewise, and inversely, I will mention opium, which, in small 
doses, is a stimulant, and which, although a stimulant, becomes 
an indirect tonic, owing to the vascular excitement which it 
determines in the organs. 

I have now reached the effects of medicaments. I have told 
you of their elementary actions ; these are mechanical, physical or 
chemical ; all this is understood. But the effects they produce 
upon the organs should be the object of a distinction, which, so 
far, has not been made. 

Among the effects, the same divisions are to be established ; 
that is, they either are physical, chemical, organic or vital. As 
an example of physical effects, you may have recourse to cold. 
As a chemical effect, you can modify the alkalinity of the blood 
by giving or withholding alkalies. 

Ordinarily, the effects obtained are of a higher order, being 
organic or vital; and these effects may also be produced by 
mechanical and physical methods. Thus, cold not only reduces 
the temperature, but determines the retraction of the vessels and 
the corrugation of the skin. It may be said that almost always 
inferior mechanical agents, or those simply endowed with prop- 
erties belonging to general physics, cause, within us, phenomena 
which are, properly speaking, of a very elevated organic order, 
and even phenomena of a vital order, since, by indirect action, 
they are able to render nutrition or disassimilation more active. 

Upon the whole, if we consider these effects which are common 
to almost all agents, and which have no connection with their 
nature, we find that those agents are really only an occasion for 
the manifestation of the phenomena which take place in our 
organs; and that they behave with regard to those more or less 
complicated apparatus, such as the nervous system, in about the 
same fashion as the finger, when it touches off a piece of 
machinery. When you fire off a gun, it is not your finger which 
causes the force of the phenomenon, no more than when you 
ignite gunpowder. 

There now remains to be made a distinction with regard to the 
effects of remedies and medicaments. 



40 PRINCIPLES AND METHODS OF THERAPEUTICS. 

There are effects which take place immediately after the ap- 
plication of the medicament or remedy, and there are others 
which are, so to say, the negative of these, and which are the 
result of predisposition. Thus, when a cold douche is thrown 
on the surface of the body, we notice that the patient, who may 
have been rose-colored, becomes pale the instant the water is 
projected on his body ; .and if it was not water, but cold air, you 
might ascertain that the patient had grown cold ; you also notice 
that he is all gooseflesh, and that the parts have shrunk. But 
this is only for an instant. If you wait a few seconds, you see 
inverse phenomena take place, redness returning, the capillaries 
dilating, the gooseflesh disappearing, and in place of the chilli- 
ness an exaggerated calorification is manifested. 

What takes place there on the surface, under the influence of 
a physical agent, also takes place in the interior under the influ- 
ence of medicaments. They give rise to phenomena which are 
direct, immediate, positive, and to other phenomena which are 
different and due to the re-action of the organism. The imme- 
diate phenomena I propose to call positives ; the other phenom- 
ena negatives of the remedies. The latter are also veiy positive, 
but nevertheless they seem to be the negative of the phenomena 
proper. To sum up, I will remind you that medicaments and 
remedies may simply produce excitation, that is, perform the part 
of the spur with regard to the steed, and determine the calling 
into play of nervous movements, or their acceleration if the 
movements already existed. But in many circumstances they are 
also the means of integrating force, and they are then what I 
have called dynamophores. Finally, in other circumstances, 
medicaments introduced into the interior of the organism be- 
have by virtue of purely chemical actions, and they form com- 
binations. This is a third and very frequent mode of action. 

But there is a fourth one, which is very interesting ; it is this : 
There are substances which, in place of merely traversing the 
organism, form combinations with the plasma, penetrate into the 
substance of the elements, live the same existence as those ele- 
ments themselves, and as long as they do, and consequently 



GENEKAL THERAPEUTICS. 41 

during a certain time, form an integral part of the organism. 
These are called alteratives. 

Among those medicaments there are some which are real ali- 
ments ; for example, iron, sulphur, manganese, cod-liver oil ; but 
there are others which are only analogous with the substances 
which enter into the normal constitution of our organization, as, 
for example, arsenic. This substance seems to take the place of 
a certain proportion of other substances which normally exist, 
and which resemble it. 

In the first lesson I could have mentioned experiments made 
by my learned friend Mr. Paul Thenard, which prove that in 
the bony corpuscles the triple arseniate of calcium may take the 
place of the tribasic phosphate. Do you notice it — arsenic and 
phosphorus two nearly-related bodies ? These experiments re- 
peated a certain number of times upon animals fully confirm 
the law which I pointed out to you in the preceding lesson. 



42 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER III. 
General Therapeutics— [Continued.'] 

Correlation of Organic Forces — The organism makes use only of the natural 
forces ; application to the action of electricity. 

All medicinal action reduces itself to an exchange of matter or of force. 

Importance of the organic substratum. Ergotine and strychnine. 

Cause of the election of organs by medicaments. 

Physico-Chemical Constitution — Phosphorus, phosphates of the alkaline 
earths, arseniate of lime, iron, salts of potash, introduction of medica- 
ments, alcohol. 

Affinity of the Histological Elements — Alcohol, ether, lecithin, protagon, mye- 
line, cere brie acid, alkaloids. 

Physical reason for those affinities — dyeing by coloring substances. 

Differences in Organic Sensibility — Extensor and flexor muscles. 

Means of Elimination of Medicaments. 

Mineral Substances : Chemical composition'.^. 
Perfect — Sulphate of soda. 
Imperfect — Oxalates, cyanides, chlorates, chlorides, iodides, bromides, arse- 

niates, salts of iron, salts of copper. 
Ill-defined Combinations. 
Unstable Combinations — Hyposulphites, hypochlorites. 



Gentlemen : 

The new method of interpreting facts, of which I spoke in the 
last lesson, supposes a close correlation between the physical and 
organic forces, since a substance taken from inanimate nature is 
capable of yielding the necessary force for the support of life. 

Force is linked to a certain material constitution of the or- 
gans. For example, in the globules of the blood in the muscles, 
in the nervous reticulations, and in the medullar and cerebral 
substances, there are functional actions which in the main, only 
depend upon the forces of nature in general. I have given you 



GENERAL THERAPEUTICS. 43 

instances winch to me seem of a kind that should carry con- 
viction to your minds. I have shown you, for example, that 
an electrical current could, for the time being, bring back volun- 
tary contraction to an organ that had lost it. This return is 
absolutely instantaneous, it lasts as long as the passage of the 
current continues, and disappears at the very instant that pass- 
age ceases. But I omitted to lay before you, at the time, the 
different methods of interpreting that phenomenon. 

Evidently the opinion might be advanced, that by the aid of 
an electric current you have simply charged the muscular ele- 
ments with extra force, and under those exaggerated conditions 
you have given occasion to rather more active manifestations of 
organic functions. But it is very difficult to understand by this 
process the instantaneity of the phenomenon. No sooner are the 
rheophores applied, than under the influence of the will the 
muscle contracts itself. This instantaneity does not correspond 
with the idea that those are mechanical or chemical actions, 
called into play by the influence of the current. However, two 
other hypotheses may be made, both in harmony with the doc- 
trine of the correlation of forces. One of these hypotheses was 
offered to me by my learned friend, Mr. Berthelot ; it is the 
hypothesis of relays. You know that in the case of a very long 
electric wire, when deperdition takes place readily in a foggy and 
damp atmosphere, it becomes necessary at the end of a certain 
number of kilometres to set up another electric machine, so as to 
facilitate the passage of the current ; these are what are termed 
relays. Thus in rainy weather it is necessary to have relays be- 
tween Paris and Rouen. 

It might be admitted that, under the conditions of which I 
spoke, that is, when the upper limb had been paralyzed, there 
was a certain degree of inconductibility in the nervous branches, 
and that, under the influence of the current, the movements 
might be communicated from the centre to the extremity of the 
nervous branches, brought in contact by that extremity with the 
muscular fibres. 

The other hypothesis, in favor of which I had decided, rests 



44 PRINCIPLES AND METHODS OF THERAPEUTICS. 

upon the possibility of restoring to a muscle, no longer making 
any, the force that it should have made. 

Whichever of these hypotheses is adopted, we must always 
acknowledge the correlation of physical and organic forces. 
Medicamental substances, and very often even remedies, (for im- 
ponderables are not medicaments,) act by yielding up force to 
the economy, or by giving matter to it. There results from this, 
that in the conflict between medicaments or remedies and the 
economy, the latter receives or loses either force or matter.] 

At first sight it will appear strange to you that it is possible 
to explain this indefinite diversity of medicamental actions with 
that uniformity of process which I suppose exists. You will 
soon see that it is not difficult to harmonize facts with this view. 
In the first place, I would have you remark that as regards the 
diversity of the phenomena which we observe, it can be ex- 
plained by the positive and negative effects of the remedies ; that 
is, by the actions they produce, and the re-actions of the organism. 

But you will understand that it is especially easy to compre- 
hend their actions when we consider the multiplicity and diver- 
sity of the organs. 

In fact, whether medicaments give force, and in consequence are 
tonics and stimulants, or if they in general are excitants, this is of 
but little moment, since at times they excite the sensory nervous 
system, and at others the motor system is concerned. They 
address themselves now to the special senses, then again to the 
general sensibility, and so forth. 

As motor stimuli, here are, for example, ergotme and strych- 
nine, which are potent agents on the motor system, and which 
probably act by giving force. But ergotine addresses itself to the 
motor system of organic life, to the smooth fibres which ani- 
mate them. On the contrary, strychnine addresses itself to the 
medullary portion. Consequently, while ergotine produces a 
contraction of the bronchise and of the uterus, strychnine pro- 
duces an exaggeration in the intensity of force manifested by 
the muscles. 

You see that, although the mechanism is identical at bottom, 



GENERAL THERAPEUTICS. 45 

by the mere fact that medicaments address themselves to different 
organs, the effects are different. I will render these facts far 
more intelligible to you by making this hypothesis : suppose one 
medicament is capable of acting on the vaso- motor constrictor 
nervous system, and another on the vaso-motor dilator, (you know 
that at the present day this division is by authority ; it was ad- 
mitted by CI. Bernard, and is by Yulpian,) if we suppose an 
effect of the same, an excitation, a cession of force being exer- 
cised on each of these two systems, the effects will be diametri- 
cally opposite. 

If you excite the dilator, a hyperemia will be the result; if, 
on the contrary, you excite the vaso-constrictors, the consequences 
will be ischsemia or anaemia, and all its phenomena with which 
you are so well acquainted. 

You therefore see that by the same process, with the same 
manner of acting, according as this action is applied to different 
organs, you will obtain the most varied effects. I deem it 
unnecessary to adduce any other examples. 

The question here presents itself: Why do certain medica- 
ments address themselves to a region, an organ, a portion of an 
apparatus, and why do others address themselves to other organs 
and other apparatus ? Why, for instance, has opium its elective 
seat in the encephalon ? Why does strychnine address itself par- 
ticularly to the medulla? Why does aconitine act on the 
expansions of the nervous system ? And why does ergot act on 
the uterus? I make no pretence at being able to give the 
reasons for these elections, but there are certain rays of light 
which can be projected upon this portion of the scientific field. 

I would have you remark that what governs the direction 
taken by remedies is, in the first place, a sort of predestination, 
which is attached to their physico-chemical constitution, and 
which causes these remedies to go and take their place, each in a 
particular tissue, and destines them to be eliminated by certain 
ducts. I repeat it, these predestinations are in connection with 
their physical and chemical qualities. 

Why is phosphorus a stimulant of the nervous system, or, as 



46 PRINCIPLES AND METHODS OF THERAPEUTICS. 

it is termed, a nervine, for this is the univocal expression em- 
ployed to designate its action ? Why, being a nervine, does it 
produce effects which at times are useful during the course of 
diseases, such as paralysis, and the different forms of tabes? 
The reason for this is very simple. 

If phosphorus addresses itself to the nervous system, it is 
because it is one of its constitutive elements, consequently it is 
very natural for the nervous system, on finding more phosphorus 
present than is contained in the food, to make use of that phos- 
phorus, and have its nutrition thereby heightened. If there is 
too much there will be excitement. Here, now, are the phos • 
phates of the alkaline earths. Why do they modify the bony 
system in cases of rachitis and osteomalacia? Why do they 
heighten nutrition in cases where it is languishing, as with 
ansemics and cachectics ? The reason is simple. Because they 
are an indispensable element in the constitution of the bone cor- 
puscles. Why do they awaken nutrition ? For the same reason. 

There are experiments proving the effective and necessary 
intervention of the phosphates of the alkaline earths in the de- 
velopment of all tissues, not only of the animal tissues, but also 
of the vegetable. It is, indeed, already a very long time ago, 
that my learned colleague, Mr. Gosselin, in company with a 
naturalist, young at that time, Mr. Alphonse Milne-Edwards, 
made experiments upon animals and vegetables which prove 
the intervention of the phosphates in nutrition. 

Wherever there is a cell, it may be said that there is a certain 
proportion of phosphates of the alkaline earths ; it is, therefore, 
natural that these phosphates should go to cells in process of 
development. Arseniate of lime may take the place of the phos- 
phate in the bones. Why is this ? Because arsenic and phos- 
phorus are elements of the same group. We come now to iron : 
why does it go to the globules? Why does it help to increase 
their number? Because iron forms an integral part of that 
coloring matter found in them, and thus is one of their elements, 
the same as manganese. 

You see from this alone, that it was predestined to act on the 



GENERAL THERAPEUTICS. 47 

blood particles, and consequently to restore them in the organism 
of anaemic or cachectic persons. 

Now, a word on the salts of potash. These salts nave some 
special effects which enable us to make use of them in certain 
morbid cases. When they are used in moderate doses they act 
as stimulants of respiration, and of the muscular function. Why 
this action on the organs of haematosis, and on those of contracti- 
bility ? It is because there naturally exists in the blood globules 
a notable proportion of potash salts, and that these same salts are 
to be found in considerable quantity in the muscles of which 
they constitute, so to say, an integral part. Owing to this, they 
are aliments for those special organs. Consequently, you see of 
what importance salts of potash are in anaemia, in saccharine and 
albuminous diabetes, and I may also add in polysarcia, for 
gout, polysarcia, albuminuria and saccharine diabetes, all belong 
to the same morbid family. 

Under those conditions, potash salts awaken activity in the 
globules, consequently they favor the functions of the muscles, 
and on that account, also, allow those which are overcharged 
with adipose tissue to burn more actively, since circulation is 
under better conditions. 

These are examples which, I think, prove to you what is the 
condition which directs the different medicaments towards such 
or such an organ, and which assigns to them in advance the 
function to be filled, either in the physiological or morbid state. 
As to the substances which do not act the part of food, which 
do not remain in the economy, but which, so to say, only pass 
through after having produced the different very fugitive phe- 
nomena which I pointed out to you, what circumstances deter- 
mine the direction taken by them — the spot towards which they 
will aim their blows ? Here they are : In the first place, there 
is the point of application of substances not called upon to per- 
form the part of foods. It is evident that if you apply a substance 
on the gastric mucous membrane, you will develop by contact 
certain phenomena, which precede all absorption, and which 
are in relation with the anatomical character of this membrane. 



48 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Do you want an example ? You introduce into the stomach 
of a person in a fainting fit a certain quantity of an alcoholic 
liquid. This liquid, by contact alone, determines the re-awaken- 
ing of all the functions, reflex action^ sympathy, as the ancients 
called it, and that, too, before the liquid has had time to be 
absorbed. This is an effect which 'is due to the point upon 
which the medicament has been applied, for, it stands to reason, 
you might have placed it on the sinciput without obtaining the 
same result. 

But there are circumstances of far greater importance than 
this ; these are the chemical affinities which exist between the 
medicaments and the histological elements, and which then 
decide on the point where an accumulation of the medicament 
will be made, and consequently towards which its principal 
effects will be directed. 

I will return to this before I leave the subject. 

I desire to add, right here, that there is another circumstance 
which also determines the election of medicaments ; I refer to the 
passages for their elimination. They are eliminated some by one 
passage, others by another, and I will show you that on their 
way they determine more or less noteworthy phenomena. 

I come now to the question of chemical affinities between 
medicaments and histological elements. Long since, medico- 
legal physicians observed facts which relate to this question ; 
long ago, my very dear friend Tardieu,! called attention to the 
smell of alcohol exhaled from the brain of men who had died 
of acute alcoholism. Since then the smell of ether has been 
observed in persons who had died from etherization. To what 
is this due ? I have advanced the opinion, which is confirmed, 
as you will see by other considerations and other facts, that 
alcohol, which is capable of dissolving a certain number of sub- 

1 Tardieu, Medico-Legal Observations on the Inebriate State, considered as a 
complication in wounds, and as a cause of prompt or sudden death. Ann.- 
d'Hyg. 1848, t. XL., p. 290. And Medico-Legal Studies upon Wounds, (Paris 
1879,) p. 109. 



GENERAL THERAPEUTICS. 49 

stances in the nervous system, attaches itself to it exactly as 
water impregnates substances that have an avidity for water. 

This same fact has been noticed under another aspect, and 
indicated a long time since by a great chemist, who committed but 
one fault — that of having become a great manufacturer — Justus 
Liebig. 

He called attention to the fact that the intermediate alkaloids 
between the fatty and resinous bodies seem to address them- 
selves particularly to the nervous system, and that in the nervous 
system essential substances are met with which seem to play a 
considerable part ; like Mr. Fremy's cerebric acid, a substance 
which is a fatty acid. 

Liebig remarked that this predilection of the alkaloids for the 
brain seemed to be connected with their analogies of constitution 
with the immediate principles of the nervous system. He ob- 
served, in fact, that the alkaloids are bodies not far removed from 
the fatty bodies. 

What Liebig said of cerebric acid might be applied at this 
day to other substances none the less essential to the nervous 
system, and in particular, to Gobley's lecithin, to O. Liebreich's 
protagon, and to the myeline of the nervous tubes. 

You understand, therefore, why it is that the alkaloids 
address themselves more particularly to those organs containing 
substances with which they have a greater degree of affinity ; 
they are, so to speak, the solvents of these in the same way as 
alcohol and ether are for the fatty substances in the nervous 
system. But we do not yet know why it is that a given alka- 
loid selects a given portion of the nervous system; opium, in 
particular, the cerebral hemispheres, strychnine the medulla, and 
aconite the divisions of the fifth pair. It is highly probable 
that this is owing to chemical affinities of the same order as those 
to which I called your attention not long ago. 

This affinity is not any more extraordinary than that daily 
observed among icterics. To what is due this coloring by 
hemapheine, or by the coloring matter in the bile ? It is due to 
a positive affinity presented by those substances for the fibrous 



50 PRINCIPLES AND METHODS OF THERAPEUTICS. 

tissue, for it is in this tissue that the coloring takes place. It is, 
so to say, a kind of organic lake, which is formed by the tissue 
and the coloring matter; exactly as you see certain coloring 
matters attaching themselves, from preference, to silk, and others 
to vegetable cellulosis. You constantly see this in micro-chem- 
istry. Why are solutions of carmine and of nitrate of silver 
used? Because these chemical substances have a particular 
affinity for a certain class of elements, for at times only the core 
is colored. It is the same with iodine for glycogenous matter. 

Suppose that those substances which are inert, which thus 
attach themselves to a certain order of elements, were at the 
same time active substances : it is clear that, thrown into the 
circulation, they would produce upon the elements considerable 
changes in their structure and in their manner of operating. 
Thus there is no difficulty in understanding those phenomena, 
which, however, are not as yet demonstrated. 

There is another point to be noticed. When we study the 
undivided action of medicaments or poisons (they are all the 
same, only differing in doses,) we are not long in noticing that 
their effects make themselves felt, by preference, on a certain divi- 
sion of the nervous system : thus, sensibility often escapes, while 
movement is affected, and that, too, more in certain regions than 
in others. 

For example, you give a medicament capable of producing 
paralysis; whatever is the nature of this agent, where will it, in 
preference, make itself felt? on the extensor muscles of the 
forearms and of the lower limbs. Is not this something very 
strange ? And here the fact is to be explained, not only by 
chemical affinities, but by organic predispositions. 

It is the same for the sensory system. Phenomena of sensi- 
bility persist by virtue of an anatomical circumstance which has 
not been sufficiently noticed, but to which I call your attention. 
Sensibility does not only exist where there are sensory nerves. 
Are you not aware that on the back of the hand there are but 
few nervous fibres ? Yet there is not a single point where in 
pricking yourself you would not feel the sting of the needle. 



GENERAL THERAPEUTICS. 51 

What is this owing to ? for it would be purely accidental had 
one always met with a nervous fibre. It is that the histological 
elements of the dermis are all endowed with a faculty, which is 
excitability, and that when their excitability is called into action, 
an excitation is gradually established among the histological ele- 
ments which are in contact. This is what Hunter termed the 
sympathy of continuity and contiguity. When this disturbance 
has reached a sensory filament, the latter communicates it to the 
nerve centre, but it has not originated in this. In other words, 
transmissions of sensibility are not only made by nervous fila- 
ments, but also by surfaces. That enables you to understand 
how, even when there is the losion of a nervous filament, there 
still remains transmission of impression, because it is trans- 
mitted by routes which are not indicated by nerve filaments 
and tubes. 

It is entirely different as regards mobility, which is connected 
with nervous ramifications in such a way that voluntary move- 
ments can only be transmitted by nervous filaments. Why this 
difference of action upon the extensors and the flexors ? A much 
greater difference than is supposed, and such that I was able to 
say, in times past, what has since been admitted, that there must 
exist in the nerve centres distinct regions for the muscles which 
extend, and those that bend the body. Well, the region of the 
muscles which extend is a region far more sensitive to all excit- 
ing or depressing agents' than the region that governs the muscles 
which flex the body. And it is because of this predominance 
that when you introduce strychnine, you produce convulsions in 
the muscles that flex and not in the others. In order to impress 
upon you these phenomena, I have but to say to you that this 
predominance of force manifests itself even in intra-uterine 
life ; to it is due the curved position assumed by the foetus in its 
mother's womb, and this predominance continues throughout the 
whole of extra-uterine life. 

Now, a word upon the influences exercised by the passages for 
elimination on the mode of action, and the elections which medi- 
caments make in connection with certain organs. Why do the 



52 PKINCIPLES AND METHODS OF THERAPEUTICS. 

essences — like essence of turpentine, of cajuput, of eucalyptus — 
exercise their influence upon the respiratory passages or on the 
skin ? It is because they pass through the respiratory passages 
and traverse the sudoriparous glands, and that on their way they 
produce the "effects of which they are capable. 

Why does copaiba produce such marked effects upon the urino- 
genital apparatus ? Because it passes through the kidneys, and 
after having been eliminated by these glands it modifies the 
mucus while on its passage. 

Why are cantharides held in such high repute in certain regions 
of the Orient? Why do they develop a factitious and short- 
lived power? Because they are eliminated by the kidneys in 
sufficient proportions to determine phlogistic phenomena. 

Chloride of potash is an effectual cure in a certain number of 
buccal affections, because it is eliminated by the salivary glands 
and those adjacent. 

You thus understand, that in cases of ulcerous membranous 
stomatitis, it can determine modifications that are favorable to 
restoring health in the glandular apparatus. 

Finally, we have emetine, that is the active principle of ipecac, 
which, when introduced under the skin, and thrown into the cir- 
culatory torrent, leads to vomiting. 

Why is this ? I am well aware there are two hypotheses ; but 
there is only one which is valid. 

The elimination of emetine takes place through the digestive 
apparatus. It does not act while it is in circulation, but when 
it is eliminated by the glands of the digestive tube — principally 
by the liver — it then reaches the intestine, as if it had been 
directly introduced there, and when the quantity is sufficient, it 
brings on nausea and vomiting. This fact, at the present day, 
is beyond cavil. Emetine, when introduced into the stomach, 
acts energetically as a nauseating emetic, in doses of gram 0.15- 
0.20. Introduced in the cellular tissue, its action is greatly re- 
duced; it becomes necessary to increase the dose, to gram 0.30, so 
as to obtain effects. If you experiment upon animals and kill 
them at the end of a given time, when they show signs of nausea, 



GENEEAL THERAPEUTICS. 53 

you will find present in the intestine emetine, which you can 
administer to another animal and cause it to vomit.l 

Here, then, are a number of circumstances showing that the 
effects of a substance are in connection with the direction it takes 
in leaving the economy in which it has sojourned but for a very 
brief period. 

I have now reached a very interesting question. It is that of 
ascertaining (since we have established that medicaments act 
chiefly from chemical qualities) to what the different remedies 
owe their properties. They owe them to the nature of the ele- 
ments which enter into their constitution; to the manner of 
arrangement of these elements, and also to a particular structure. 
You know what is understood by structure in chemistry ? It is 
evident that if you simply take oxygen or nitrogen, they act in 
a different manner. It is the same if you take substances like 
arsenic and phosphorus ; therefore the nature of the elements has 
a considerable influence on the actions of medicaments. But 
there is also the manner of combination affected by these elements, 
and-you will see in the next lesson that there are facts of great 
interest which would be unexpected had they not for a long time 
been recorded by science. I say that combinations also introduce 
great differences in the manner of acting of substances which 
only act as chemical bodies. We may, here, distinguish three 
cases: 

1. Cases in which combination is so perfect that elementary 
actions disappear. In sulphate of soda it is neither the sulphuric 
acid nor the soda which acts; it is an inoffensive salt that has a 
part to perform in the circulation, and which, when introduced 
in sufficient quantity, produces the effects with which you are 
acquainted. 

2. There are cases in which combination is not so very perfect, 
but that there is a certain group of elements which will impress 
its stamp upon the medicament. And here, there are two orders 
of facts. At times it is a neutral body, at others an acid body, 
that predominates, or else it is the one which performs the part 

*. All these very conclusive experiments have been made by Dr. d'Ornellas. 



54 PRINCIPLES AND METHODS OF THERAPEUTICS. 

of base. For example, when you have to deal with oxalates, 
oxalic acid is the dominant, and it is this acid which impresses 
its stamp upon substances. Hence, oxalates owe their activity 
chiefly to oxalic acid. Cyanides are in the same category j it is 
cyanogen or cyanhydric acid which ogives them their therapeutic 
and poisonous properties. 

So, also, with the alkaline chlorates and chlorides, the bro- 
mides and iodides, with arsenic aud the arseniates ; in such a 
way that in all those cases predominance is with the metalloids, 
which always act the electro-negative part, or with the acids 
when acting that part ; in the other cases it is with the bases. 

Whenever, in the place of alkalies, you have to deal with 
metals properly so called, it is these that in a general way will 
have the greatest influence over the physiological actions of the 
medicament. Thus, whatever acid is combined with iron, it is 
the latter which predominates. Whatever acid is combined with 
copper, it is the copper; with mercury, it is the mercury. I 
might add baryta, but it is no longer used, so I need illustrate 
no further. But there are also circumstances in which things do 
not happen as I have just stated. It is when we have to deal 
with weak combinations. It is evident that when you are in 
the presence of an excessively acid salt, chemically so speaking, 
you may consider the acid as free ; likewise, with very basic salts, 
you may look upon the base as free. 

3. Finally, there are other cases. If you have to deal with 
hyposulphites and hypochlorites, it is no longer precisely either 
the acid or the base which possesses influence, but their derivatives. 
Thus, hypochlorites liberate, on the one hand chlorine, on the 
other oxygen, and in consequence they act by means of these two 
elements. 



GENERAL THERAPEUTICS. 55 



CHAPTER IV. 
General Therapeutics— [ Continued,'] 

Organic Substances : Simplicity of composition. 
Nature of Elements — Anaesthetics, hydrocarbons. 
The Part of Nitrogen — Exceptions : Picrotoxin, duboisine, morphine, tea, 

coffee, coca. 
Molecular Grouping — Starch, gum, dextrine, vegetable and animal glycose, 

glycocol, benzoic acid, nitrous ether, nitrite of ethyl, cacodylic acid. 
Chemical Composition — Curara and stiychnine, apomorphine. 
Conveyance of Medicamental Action — Imbibition, capillarity, contagion, reflex 

action, liquefaction. 



Gentlemen : 

It is the substances belonging to the mineral order that pre- 
sent the peculiarities I pointed out to you in the last lesson. 
Among substances of organic origin, matters are far from taking 
place after that fashion. When you consider the disparity which 
exists in the action of the different substances belonging to the 
vegetable kingdom, on the one hand, gum, sugar and starch, on 
the other, alkaloids and glucosides; the one, inert substances, 
the others possessed of a violence of which we can only form an 
idea when we think of dynamite; when you compare this 
greatly varied spectacle, you at once understand that the nature 
of the elements entering into the composition of those organic 
substances has but little importance, and that it is the modes 
of arrangement, the combinations, which possess the greatest 
weight. 

In fact, as you know, organic substances are formed upon 
three or four ever-similar elements to which other accessory ones 
join themselves : they are oxygen, hydrogen, carbon and nitro- 
gen. How can we understand that with such simplicity of 



56 PEINCIPLES AND METHODS OF THEEAPEUTICS. 

chemical constitution there should be such vast differences in 
their actions ? 

The nature of the elements in organic substances should cer- 
tainly be taken into consideration, but I will show you that the 
most important part rests with the mode of arrangement of those 
elements. 

It has been observed that the compounds which act the part 
of anaesthetics, and which we make use of in surgery and medi- 
cine, are substances which almost all resemble one another, and 
are very closely allied. They are more or less hydrocarbons, 
that is, bodies in which one or more molecules of hydrogen may 
be replaced by molecules of simple bodies, or of chlorine, as in 
chloroform. But, as a fact, they have always about the same 
composition — that is, hydrogen and carbon. Those substances, 
however, all have the property of removing sensibility, and con- 
sequently pain. It is possible to go even further, and assert that 
all hydrocarbons are more or less anaesthetic. You see that the 
nature of the constituents exercises a great influence. 

I will right here give you the proof of this proposition. You 
all know the effects produced. by bouquets of flowers kept within 
closely- confined spaces. These fragrant emanations are noxious ; 
the gravest results may arise from them, extending at times 
up to apparent death, if the room is small and the flowers highly 
scented, as in the case of tuberoses. Well, those emanations are 
nothing else than hydrocarbons which are being evolved. 

The same may be said of the emanations from hops. You 
have only to lay a child on a bed made of hop blossoms : it will 
be put to sleep, it will be anaesthetized. Oil of turpentine, of 
such constant use in the painting of houses, is also an anaesthetic 
of great power, so much so that men who work in closed rooms, 
who sleep there, are often the victims of serious disorders. 
They fall into a state of somnolency, after having experienced 
headaches and vomitings— in fact, all the phenomena attending 
poisoning. 

Take notice : here again there is hydrogen and carbon. No 
doubt chemical constitution has an influence here, since there are 



GENERAL THERAPEUTICS. 57 

but two simple bodies combined to produce the same effects ; but 
there also exists an influence, due to a particular arrangement of 
the molecules, as you will presently see. 

In order to show you what may be the influence of chemical 
constitution, there remains for me to say that the most active 
substances are nitrogenized substances; these are the alkaloids. 
No doubt among neutral substances there are bodies which 
do not contain any nitrogen, and yet possess great energy, and, in 
advance, you all have digitalis present to mind; but, at any 
rate, we must admit that almost all substances of great power 
are nitrogenized substances. 

Chemists admit that it is around molecules of nitrogen that 
molecules of other simple bodies group themselves so as to pro- 
duce the arrangement from which will result, for example, a 
molecule of aconitine. 

But here, again, too much importance should not be given to 
nitrogen, for if nitrogen, as a simple body, exercised a prepon- 
derating influence, the intensity of action of substances would be 
in relation to the proportion of nitrogen in the molecules. 
Such, however, is not the case. I might mention to you picro- 
toxine, which is one of the least nitrogenized, yet most violent 
of poisons. 

To this I could add duboisine, an alkaloid obtained 
by Mr. Petit from an Australian plant, Duboisia miropioides, 
belonging to an intermediary group between the solanese and the 
scrophularinse ; it is a substance allied to atropine, and which, 
notwithstanding its violence, contains but little nitrogen. Mor- 
phine, which is less violent, and which, in place of being given 
in doses of one milligramme, is used in doses of several centi- 
grammes, contains more nitrogen. The proportion is much 
greater in quinine and its derivatives. Finally, those alkaloids 
extracted from substances which I have called dynamophoric, 
and which are used in therapeutics and as food, such as tea, 
coffee, coca, are all alkaloids the most nitrogenized and yet the 
least violent. Thus you see that here, again, we cannot connect 
intensity of effects with the nature of the elements. 



58 PRINCIPLES AND METHODS OF THERAPEUTICS. 

It therefore becomes necessary to interpose molecular arrange- 
ment, and especially so when we consider isomeric bodies. For 
they are not only constituted out of the same elements, but in 
the same proportion, and yet they are endowed with the most 
varied properties. 

For example, here are starch, gum and dextrine, which have 
in common the formula of C 12 H10 01°; they are isomeric, 
but very different substances. 

Again, the hydrocarbons, while differing so much from one 
another in properties, appearance and molecular weight, are all 
constituted about alike. It may be said that in almost all the 
essences, from essence of lemon, and turpentine on, the same 
constitution always prevails — CH, or multiples thereof. Gradu- 
ally, as these molecules become heavier, the substance is found 
losing its volatility and gaining in specific gravity. This ena- 
bles you to understand how molecular grouping exercises its 
influence on the organoleptic properties. 

Here is another example : the two kinds of glycose — vegetable 
glycose, which is the sugar of certain vegetable products, and 
animal glycose, diabetic sugar — are both expressed by C 12 H 12 
O 12 ; but what a difference between those two substances ! 
While grape sugar injected into the circulation of a dog shows 
itself in the urine, on the contrary, diabetic sugar injected into the 
same medium will remain in it as one of its elements, exactly as 
if it had been formed there by the organism itself. But the 
animal will not become diabetic. The difference is even still 
greater when we compare glycose with acetic acid ; we find the 
same composition, the same elements in the same relations, and 
yet what a difference between sugar and acetic acid ! Here is a 
third series : glycocol (C 4 H^ N O 4 ), which must be known, 
because this substance acts a considerable part in very many 
therapeutic phenomena. When mention is made of benzoic 
acid, one cannot avoid speaking of glycocol. Well, nitrous 
ether and nitrite of ethyl have the same composition as glycocol, 
and may become poisonous. 



GENERAL THERAPEUTICS. 59 

Here is a more surprising case : You all know the effects of 
arsenious acid, so much used as a poison, especially in former 
times, when the method of ascertaining its presence in a dead 
body was unknown. Arsenic, so violent when in a free state, 
loses all activity when it is made to enter into a combi- 
nation called cacodyle. Cacodylic acid, which contains 54 per 
cent, of arsenic, can be introduced in enormous quantities in the 
economy, without any ill effect. You see that here we have 
evident demonstration that owing to a peculiar mode of combina- 
tion, properties pertaining to elementary matter may be concealed, 
in the same way that a while ago I showed you that new modes 
of arrangement give rise to properties which did not previously 
exist. 

Elementary composition is therefore absolutely insufficient to 
explain the properties of medicaments and their diversity of 
action. Shall we, then, take into account chemical constitution, 
and shall we attach to that structure all the importance we have 
been obliged to withdraw from elementary constitution ? 

This is a point in the history of therapeutics on which I am 
obliged to dwell, because it has been made conspicuous in a cer- 
tain number of recent French and foreign works. As early as 
1841, Black, an English chemist, said that molecular structure 
alone is of importance in medicaments. He endeavored to de- 
monstrate that substances might differ greatly in their constitu- 
tion, but owing to the fact that they were isomorphous, they exer- 
cised the same therapeutic action. He had evidenlty forgotten that 
substances which crystallize in the same form are already sub- 
stances of nearly analogous elements. For example, let us take 
the hyphosphate of lime and the tri-arseniate, which are isomor- 
phous. I have shown you that this last enters into the bones and 
takes the place of the hyphosphate. But to what is this due? 
Not because they are isomorphous, but because their constituents 
are analogous. Therefore, it is not isomorphism which causes 
identity of physiological action ; this last is due to fundamental 
analogies between the elements of bodies that are isomorphous. 
Consequently, you see that it is impossible to rely solely upon 



bV PRINCIPLES AND METHODS OF THERAPEUTICS. 

structure, for isomorphism indicates molecular structure in the 
same way as the several fragments of a column are expressive of 
the column in its entirety. 

There are structures which, although similar, have considerable 
difference in their physiological and therapeutic action, while 
again, there are dissimilar structures with considerable resem- 
blance as regards these same actions. It is, therefore, impossi- 
ble to give that importance to Black's opinion which he supposed 
it deserved. 

But there are experiments of a most interesting kind, which 
bear upon capital points in therapeutics, and which will show 
you how secondary is structure in a certain number of cases. 

These experiments are those made almost simultaneously by 
Crum-Brown and Thomas Fraser, in England, and in France 
by Jolyet and Andre Cahours. They establish this : That in a 
molecule of an alkaloid, (let us take quinine, strychnine or mor- 
phine,) one or more atoms of hydrogen may be replaced by one 
or more atoms of ethyl or methyl, without changing the struct- 
ure of that molecule. If Black's opinion was well founded, there 
should not be any noteworthy change in the physiological action 
of that molecule, which remains what it was, as regards its 
structure. Well, not only is the action no longer identical, but 
it is at times the reverse of what primitively existed. 

One of the principal alkaloids upon which the French and 
English experimentalists, almost at the same time, (the first pub- 
lication was, however, by Fraser,) made investigations, was 
strychnine. They substituted molecules of ethyl for the hydro- 
gen of this alkaloid, and in that way obtained new alkaloids, 
among which was eihylostrychnium. They experimented upon 
them, and observed the widest differences between them and the 
original alkaloid ; differences which, at times, amounted to the 
most absolute antagonism. 

But what is of especial interest to us is what takes place with 
regard to strychnine. In experimenting with ethylostrychnium 
it was found that in place of having an agent producing con- 
vulsions and tetanus, we had, on the contrary, a substance which 



GENERAL THERAPEUTICS. 61 

paralyzed the motor system, by acting particularly upon the 
peripheral extremities of the motor nerves. Now, remember 
the beautiful experiments made by CI. Bernard upon curara, and 
you will see that it has exactly the same manner of acting. This 
is the more remarkable because travelers had informed us that 
curara was supplied by lianes belonging to the genus Strychnos. 
The principal strychnias employed are the strychnos toxifera, col- 
ubrina and castellana. 

According to the report of travelers, the natives boil these 
lianes in a kettle, and from the residuum, at the end of more or 
less time, they obtain the curara. But how is it that by this 
operation a strychnos, which is an agent producing tetanus, should 
be converted into a paralyzing substance ? 

Now that we know that so slight a modification in the compo- 
sition of strychnine suffices to change it from an agent producing 
tetanus into one producing paralysis, we understand how it is 
possible that the alkaloids of the strychnos can be so modified in 
the operation to which they are submitted by the natives, as 
to be converted into ethylostrychnium. This idea of similitude 
between curara and strychnine, which I advanced long ago, has 
been adopted by Fraser himself. 

I must add, however, that the analyses which have been made 
of curara do not aid in demonstrating any identity between 
ethylostrychnium and the active principle in curara. But the 
differences are so very fugitive, that unless great delicacy of 
manipulation is observed they are not noticed. 

There are also analogous facts for morphine. Morphine is 
one of the most powerful of hypnotics. All that is necessary is 
to take from it a molecule of water to convert it, without change 
of structure, into apomorphine, which is an emetic substance. 
This change amounts to so little, that it has but to be placed 
under favorable conditions to be again transformed into mor- 
phine. Clearly it cannot be said that properties are attached to 
molecular structure. 

I add, without delay, because it is an interesting point, that 
sanguinarine, which is the alkaloid of a papaveracese, contains 



62 PRINCIPLES AND METHODS OF THERAPEUTICS. 

an active substance, which possesses precisely the properties of 
apomorphine, as if, in the papaveracese family, there was a par- 
ticular structure for active principles, and that this structure gave 
rise to morphine in the poppy, and in the neighboring plants to 
an active substance which reminds us of morphine when stripped 
of a molecule of water. 

Upon the whole, when we recapitulate the causes for modifica- 
tions of a chemical nature, which exert a more or less consider- 
able influence upon medicaments, as regards their action, we see 
that particular weight should be given to elementary constitution 
and to molecular grouping. Some weight should also be given 
to structure, which usually takes place around the nitrogen when 
organic compounds are concerned, as, also, to the state of dyn- 
amization of the compounds in question. 

I now proceed to the study of the means, by the aid of which 
medicaments are able to diffuse their action throughout the whole 
economy, while their application has only taken place upon a cir- 
cumscribed point. What are the means of diffusion for medica- 
mental actions ? These means are various, and I shall now re- 
view them in succession. 

Let us first find the conveyance of the medicament, then the 
propagation of the effects which the medicament has produced 
upon the point with which it has been in contact. The convey- 
ance of active principles is accomplished by quite a variety of 
mechanisms. For example, when you introduce into the corner of 
the eye a drop of a concentrated solution of atropine, you soon 
notice that the whole of the eye is wet, and that in consequence 
there is a dissemination which enables the medicament to be 
absorbed by a more extended surface. In the same way, when 
you introduce a medicament into the alimentary duct, it is at first 
received in the mouth — the vestibule of the digestive organs. If 
it is not very soluble, it may go through the whole extent of the 
digestive duct. Let us suppose that this substance is introduced 
into the cellular tissue. Here there is a sort of imbibition by 
capillarity. You notice a diffusion of the liquid taking place under 
the skin. If you introduce the substance under the hide of an 



GENERAL THERAPEUTICS. 63 

animal that can be killed, you observe that at a given moment 
the substance has spread itself in a circle of greater or less ex- 
tent, according to its diffusiveness, and the conditions of the 
tissue in which it happens to be. These phenomena are pro- 
duced by means of what is called capillarity, and also by means 
of osmosis, endosmosis and exosmosis. 

You see the histological elements of the different tissues load- 
ing themselves with active principles. When these active prin- 
ciples disseminate themselves, in the same way as in the sub-cu- 
taneous celluar tissue, they meet with capillary vessels of all 
kinds ; veins, lymphatics, arteries. They are then absorbed, and 
when once absorbed they circulate through the whole organism 
and lodge in different organs, according to their affinity. Here 
there is a mode of diffusion for active substance, first by imbi- 
bition, later by circulation. 

We shall now see how actions which have been exercised on a 
given point are propagated, when the active substance is not dis- 
seminated in the economy. These actions are propagated by 
virtue of what the ancients called sympathy. But, wishing to 
account for these phenomena, we have gone further, and it is here 
that we have to call in the law of reflex actions. For example, 
you apply a sinapism. Its active substance is not absorbed, yet, 
for all that, if it has been applied to a patient in a swoon, you 
will see the patient reviving and opening his eyes. By what 
process has this phenomenon been produced? Through the 
medium of a reflex act; first pain, then an impression upon a 
sentient nerve on the cutaneous periphery ; conveyance of this 
impression to a nerve centre and excitement of the latter ; then 
return of the excitement towards the heart. When you intro- 
duce into the stomach of a patient in a fainting-fit a spirituous 
liquid, before it is absorbed the patient is revived. It is by re- 
flex action that the propagation and generalization of the local 
effect produced upon the gastric membrane has been made. 

Another means is what Hunter called the sympathy of con- 
tinuity and of contiguity. That is, sympathy between two por- 
tions of the same organ, or else between two organs which are in 



64 PKINCTPLES AND METHODS OF THEKAPETTTICS. 

contact one with the other. Nothing is easier than to understand 
this class of sympathetic phenomena, when, for example, we 
study the progress of inflammation. You know to what extent 
inflammation has been discussed ; some interposing the lymphat- 
ics, and others resting their case upon venous continuity, and 
others, finally, upon the nerves. None of these opinions explain 
the facts in the case. How are we to understand these circular 
inflammations brought on by any cause whatever? How are we 
to understand this regularity of circular development, when the 
point at issue is the parenchyma of a spherical surface, with the 
aid of vessels following a determined direction ? I will say as 
much with regard to the nervous system. When you have ap- 
plied an irritating substance upon a peripherical region, the irri- 
tation spreads from place to place, from element to element, as if 
there existed in that region a sort of equilibrium of tension or 
of force between the different elementary parts of the tissues, 
which is the reason that when you have excited irritation in the 
one, the other takes part in it. In this way you can understand 
how it is possible for irritation to extend in a circular form, and 
how, losing its intensity in the ratio of the square of the radius, 
there comes a point where it is no longer perceptible. Here, 
then, is a mechanism by the aid of which you are able to account 
for certain physiological actions. 

This mechanism is not very rare. It is rather difficult to 
demonstrate, but we are conscious that it exists. Here, for ex- 
ample, is a case : You make use of poultices for a deep-seated 
pain in the stomach. You must have a reason to give, in order 
to explain their action. Poultices, as many other topics, are 
means of occlusion, capable of sheltering a portion of the peri- 
phery from the influence of exterior agents, and they act, not 
only upon the very spot on which they are applied, but also over 
a more or less remote extent. It is enough, in fact, to have 
placed the peripehery under particular conditions as regards the 
state of tension, to secure that from place to place a like state 
will reach the parts which are more or less in connection with 
the point in the periphery upon which you are acting. 



GENERAL THERAPEUTICS. 65 

Trousseau often said that it was possible to cure extended affec- 
tions, inaccessible to our local or topical agents, by only modify- 
ing a portion of the diseased part. He had no hesitation in say- 
ing that when we had to deal with inflammations of the post- 
pharyngeal tract, which extends to near the oesophagus, with gran- 
ulations, and with tubercular ulcerations, it was enough to modify 
a portion of the surface, that is accessible to our eyes, in order 
also to modify the rest. This might be expressed in this wise : 
As there is a contagion of disease, so is there a contagion in cures. 
If you soothe a part of a region, by that very act you soothe the 
whole of that region. 

As the chemical medicaments can only exercise their action by 
contact, many actions cannot be exercised, except through the 
diffusion of active principles in the economy, and not by the 
agency of the sympathy. It follows that contact should be immedi- 
diate between the acting substance and the organ which is to re- 
ceive its impression. Absorption is, therefore, a general condi- 
tion for the modification of organs by the agents which we bring 
in contact at times with the skin ; then, again, with the mucous 
membranes. What, now, are the conditions for medicamental 
absorption? The liquid state or possible liquefaction is almost 
a sine qua non. You will observe that I do not say solubility in 
water. I speak of the liquid state, because there are fatty liquids 
which are immediately absorbed. 

You know that those liquids are directly absorbed by the intes- 
tinal villi, at the summit of which there are sorts of funnels, formed 
by wide epithelial cells. In these cells the fatty matters are re- 
ceived, and they go through them to pass into the underlying 
vessels, in the same way that you effect the filtration of a fatty 
substance through a filter, provided you have first moistened the 
latter with oil. I was, therefore, right in saying that it was 
liquidity and not solubility which was necessary. 

Substances soluble in water are those most readily absorbed, 
but there are a great many which seem insoluble in it, and which 
yet are absorbed. In fact, there exists in the prima? viae a certain 
number of chemical princioles which favor the solution of differ- 

E 



66 PE1NCIPLES AND METHODS OF THEKAPEUTICS. 

ent substances destined to become medicaments Thus, in the 
stomach, bases meet with acids; acid substances find bases. In 
the second portion of the digestive duct there are salts, such as 
chloride of sodium, and it is here that Mialhe's beautiful experi- 
ment finds a place. There are, above all, fatty substances, which 
favor the solution of sulphur, of phosphorus, and even of arsenic. 
Finally, there is also albumen and albuminoidal matters. One 
can form no idea of the power these last substances have over 
others which are insoluble, even when they have been freed from 
chlodide of sodium, from the mere fact that an agent meets with 
mucus, or with albumen, dissolution sets in, within a more or less 
short space of time, and this is one of the best methods for favor- 
ing solution. 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 67 



CHAPTER V 
Avenues for the Introduction of Medicaments. 

Solvent Action of Albumen. 

The part of Gravity in Absorption — Gingival deposits, tattooing 

Avenues for Introducing Medicaments : Digestive Tract — The mouth, 
infantile syphilis, neuralgia of the fifth pair. 
Stomach — Inconveniences of this method. — Decomposition of medicaments 
in the stomach. 



Gentlemen : 

At the close of the last lesson I spoke of albumen ; there is, 
indeed, a circumstance which has been but recently known, and 
which plays a most important part : it is the solubility of a great 
number of substances insoluble in water, in albuminoidal pro- 
ducts, such as the album3n, properly so called, and the mucus, 
which may be met with in the prima? vise. Wherever albu- 
minoidal substances are found, they are great solvents of matters 
•which, by themselves, are absolutely insoluble. Thus metallic 
mercury may be dissolved in albumen and in analogous sub- 
stances. You see that the number of solvents which can facili- 
tate absorption is very considerable, and, above all, these solvents 
may be everywhere found. 

But is it only dissolved substances that can penetrate into the 
circulation and be carried along by it? No; there are solid 
substances which may be and which are absorbed in a solid state. 
This is, I admit, more a matter of curiosity, but it nevertheless 
deserves some consideration, because there are interesting particu- 
larities attached to it. 

Eabbits have been fed by mixing a great deal of charcoal in 
their food j and after a certain time it was observed that charcoal 



68 PRINCIPLES AND METHODS OF THERAPEUTICS. 

was present in their pre-vertebral and mesenteric ganglions. 
These experiments are easier when carried oat upon that unfor- 
tunate frog, the habitual victim of our experiments. Thus, 
when it is fed upon starch, to which particles of charcoal have 
been added, the charcoal is shown almost all through it; it 
finally becomes pigmented throughout almost all its tissues. 

These experiments have been regularly made by Osterlein. 
At a later date they have been continued by Eberhard, by Kdl- 
liker, whose name is well known to you, by Meyer, by Donders, 
and finally by Mensonides. They all obtained the same results. 
It is therefore evident that solid substances may penetrate into 
the vessels. 

At first sight it is difficult to understand this passage, but after 
a little reflection it is clear that there is nothing very surprising 
about it. Look at the gingival line which shows itself among 
workmen exposed to the emanations from lead. The lead parti- 
cles reach gums which are more or less soft, which among work- 
men are often bleeding, they are deposited there, penetrate from 
their own weight, and are finally enveloped by the tissues as the 
gradual organic renovation progresses. This process unfolds to 
us the way by which solid particles may penetrate into the ves- 
sels. The particles are deposited upon a given spot, they are 
finally enveloped by the tissues aud can then circulate to such an 
extent that when the operation of tattooing is practiced the col- 
ored substances, either red or blue, show themselves in the axil- 
lary ganglions ; while the tattooing was practiced upon the fore- 
arm, the only way they could reach there was through the circu- 
lation. But this is not a practical method of causing medicinal 
substances to penetrate into the organism, and besides, this might 
cause emboli in those parts where circulation is more difficult. 

In short, without considering fluids other than those which 
are aqueous, it may be said that the substances which best pene- 
trate by absorption, are those which, in the first place, are soluble 
in water, or miscible with water. 

I have now reached one of the most interesting questions for 
us : it is that of the avenues by which medicaments may be 



AVENUES FOE THE INTRODUCTION OF MEDICAMENTS. 69 

introduced. A distinction is to be established between the place 
of application and the avenue of introduction. 

Medicaments can be placed almost anywhere, on conditions of 
having instruments which can penetrate with more or less facility. 
But we should only call avenues of introduction those which in 
an intentional or accidental way are open to medicaments. 

But we must acknowledge that where we only wish to pro- 
duce topical effects, we may also produce general effects. Thus 
it is that when you will treat secondary or more or less advanced 
syphilitic lesions by mercury applied topically, you must be on 
your guard against absorption. For if the surface is of sufficient 
extent, it may happen that you will superinduce stomatitis. 
Consequently, place of application and avenue of introduction are 
two things which are often confounded. 

The avenues of introduction of medicaments may be divided 
into five categories. The mucous membranes are most used for 
this purpose. They are divided into the digestive duct, the 
respiratory organs, the uro-genital apparatus, the visual apparatus 
and the auditory apparatus. 

I have placed the digestive duct at the head of the list because 
it is the most convenient and open to use. We find there the 
mouth, the stomach, and the rectum. 

In the respiratory apparatus we have the nasal fossa, which is 
a place of absorption of far greater importance than supposed, 
many cases of poisoning having taken place from collyria, sim- 
ply because they passed into the nasal fossa by the lacrymal 
points. We also have the bronchise and the alveoli of the lungs. 
There is at present quite a fashionable method, and a very inter- 
esting one, which addresses itself to this way of introduction — 
it is that of inhalations or inspirations of vapors or liquids in an 
ethereal form. 

With the uro-genital apparatus we have absorption through 
the ureter, the bladder, and the vagina ; with the eye, by the 
conjunctiva and the cornea; with the ear, by the meatus, the 
Eustachian tube, and the drum of the tympanum. 

Another large surface, equally open for absorption, is the 



70 PKINCIPLES AND METHODS OF THERAPEUTICS. 

cutaneous periphery. Several conditions are to be considered, 
according as absorption is to take place through the unimpaired 
skin or not. If the skin is unimpaired, we then have to con- 
sider a few modifications ; either we are satisfied with applying 
medicaments to its surface, or else, on the contrary, w r e follow 
very ancient processes which have been methodized at a later 
date — one is, that by frictions we succeed in forcing open the 
pores of the epidermis, and thus bringing the dermis to absorb 
substances which could not have penetrated otherwise. A second 
process is absorption by the denuded skin, that is, the endermic 
or diadermic method. This method enjoyed great populartiy, but 
at the present day it has nearly gone out of use, having been 
replaced by the hypodermic method, which consists in the intro- 
duction of the substances into the sub-cutaneous cellular tissue. 
Yet another method is that inaugurated by Lafargue de Saint- 
Emilion. He introduced the substances into the dermis. It 
might be called the infancy of that method which we designate 
by the name of hypodermic. This plan has had antecedents, 
although it appears recent. It was preceded by the plan of 
creating an artificial cavity, in which medicamental substances 
were deposited in the cellular tissue. Thus Trousseau made 
incisions and deposited on a level with the origin of the sciatic, 
the value of a pea of belladonna or opium, which were his 
principal agents. 

No doubt this already belonged to the hypodermic method, 
but it was of a most primitive kind, and did not possess the 
value of that very elegant method founded by Pravaz' practice. 

We also have another method which has been so thoroughly 
modified by one of my former students, Mr. Luton,! that we may 
say it belongs to him. He had the idea of introducing medi- 
cinal substances at times in parenchymas, then again in deep- 
seated regions, as in deep-seated cellular tissue of a limb, in the 
ganglions and the thyroid gland. This method is called the 
method of parenchymatous substitution. The author employs it, 

1. Luton on Sub-cutaneous Injections with Local Effects, Paris, 1875. 



AVENUES FOE THE INTRODUCTION OF MEDH AMEN P8. 71 

especially in producing inflammatory effects, which induce tin- 
destruction of parts which were the seat either of an induration 
or of a chronic inflammation. But also when, by this method, 
absorbable substances are introduced, they produce diffused and 
generalized effects, and on that account it deserves a place here. 

At times sores and fistulas are used as avenues of introduction. 
Thus, chloral has been introduced into fistulas, and the pains 
have been allayed. In the same way, tincture of iodine has 
introduced, and not only has a modification of the s 
brought about, but also an absorption of iodine, which is of 
benefit to those troubled with scrofulous affections. The serous 
cavities would prove useful, but for this drawback : that they 
are highly irritable, and thus give rise to phenomena of the 
greatest gravity, as, for example, when the peritoneum is 
concerned. 

Although medicinal absorption through serous cavities has 
been observed, it is not a plan that can be recouimendrd. I 
speak of this because, when iodine has been introduced into an 
articular serous cavity, phenomena of more or less intense iodism 
have, at times, been witnessed. 

Mention may also be made of the introduction of active sub- 
stances into the vascular system, in the veins and tin- ai 
This is what is called transfusion. This method already dates 
two centuries back. It was at first practiced upon animals, then 
upon man. It was not so much medicamental substances that 
were introduced as blood — at times, that of animals, then, again, 
human blood, when it was necessary to revive more or Irs- debili- 
tated patients. This operation dates back to 1665, upon animals, 
and to 1677 on man. 

These are exceptional means, and I say to you in advance that 
I do not, in the least, approve of the introduction into the veins 
of substances capable of producing sleep. These are dang 
methods, and they have shown their effects by phenomena of the 
most serious nature. 

The above are the several means of introducing medica- 
ments. I now have to speak to you of the principal one That 



72 PRINCIPLES AND METHODS OF THERAPEUTICS. 

is, of the administration of medicaments through the digestive 
organs. 

I commence by the mouth. It is a part of the digestive duct, 
which, at first sight, seems to you of but little avail for medici- 
nal purposes. It is a part where the epithelium is very dense, 
and it is also a thoroughfare. Nevertheless, the mouth is an en- 
trance door which is not to be overlooked. By its agency it is 
possible to obtain the absorption of medicinal substances, which, 
by other processes and other ways, would be with difficulty 
absorbed. For example, through the mouth we can obtain the 
absorption of liquid and solid substances, which otherwise would 
be of difficult deglutition. Solid substances are applied to the 
mouth by the aid of frictions. They are spread on the more or 
less extended surface of the inner side of the cheeks and under 
the tongue. The quantity of substance thus deposited, by reason 
of its nature, is sufficient to act, and in a certain number of cases 
excellent results are obtained. 

Thus, in the event of syphilis among new-born children, it is 
very difficult to make them take medicine. On an emergency, 
some of Van Swieten's solution might be mixed with milk, but 
often children refuse everything else but the breast. In such a 
case it is an established custom to practice frictions on the in- 
terior of the cheeks with proto-iodide of mercury, and the quan- 
tity thus absorbed is sufficient to cure the syphilis. Formerly it 
was permissible to administer to the nurse the medication which 
was to cure the child, but this cannot be done at the pres- 
ent day with the modifications which our ideas of morality have 
undergone, unless it be that the nurse is also the mother. We 
have not the right of treating a hired nurse for a disease 
which she has not. 

There are also circumstances in which generalized effects are 
not needed, but where localized ones are desirable. For ex- 
ample : In neuralgias of the fifth pair, very often a bit of raw 
cotton impregnated with ether or chloroform is placed between the 
dental arch and the cheek. In analogous conditions, Trousseau 
even used extract of belladonna. As to the stomach, I have no 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 73 

hesitation in saying that there exist, on the nature of stomachic 
absorption, illusions, which have been completely destroyed by 
experiments conducted in due form. Indeed, it is not an absorb- 
ing organ, absorption only taking place in it in a slow and diffi- 
cult manner. You have only to reflect upon the condition, in 
which it finds itself, either when it is in a state of vacuity or 
when it is full. In vacuity, the stomach is in a constant state 
of desquamation, which forms on its internal face a gelatiniform 
coating, and this goes on increasing in the intervals between meals. 
If there is a saburral condition, an enormous mass of this Bab- 
stance is found covering the lining membrane, so that a medici- 
nal substance happening to fall into such a stomach, onlv with 
great difficulty finds the means of placing itself in contact with 
the absorbing surface. Alimentary residues are also often found 
therein. Even among healthy people it is not rare to find these, 
from four to six hours after a meal. There are also ferments of 
various kinds; also acids, which, in certain cases, are injurious 
to medicaments. Finally, the stay of substances in the stomach 
is, of necessity, a prolonged one, and this sojourn which appears 
favorable to absorption becomes unfavorable, when there are 
present ferments, etc. Under these conditions, medicinal sub- 
stances which have penetrated into the stomach, and which re- 
main there, may become deteriorated. Consequently, pose 
a better knowledge of the physiological conditions of the stomach, 
we are able to understand why it is a questionable avenue for 
absorption. 

I stated that experiments had given prominence to this inferi- 
ority of the stomach. One of these, due to Claude Bernard, conr 
sists in the introduction into the stomach, after ligature of the 
pylorus, of a more or less dilute solution of b try ch nine. 
So long as the pyloric orifice remains closed there is no tetanus, 
nor are there convulsions produced by this alkaloid. Bui if the 
ligature is slackened, in a few minutes the phenomena of tetanus 
are induced. 

The substances had not been destroyed by the stomach, as could 
be proved by taking some of the liquid contained in this Btomaoh 



74 PRINCIPLES AND METHODS OF THERAPEUTICS. 

and giving it to another animal ; this last would experience all 
the symptoms of convulsing alkaloids. 

It is evident that the degree of resistance to absorption will 
vary according to the nature of the substance presented. Thus 
there are observations, already rather old, which prove that water 
is readily absorbed, while there are others which show that sub- 
stances which are extremely dyalizable, such as yellow prussiate 
of potassium and iron, are also absorbed with comparative 
ease; others, among which is curara, are absorbed only with 
great difficulty, and which, in consequence, should not be 
entrusted to it. 

I could again recall to you here an experiment made by CI. 
Bernard. He showed that when the mucous membrane of the 
stomach was uninjured, curara could be introduced into it with- 
out causing any of the accidents to which it gives rise when 
thrown into the vascular system. When it is introduced into the 
stomach filled with food, at first sight it would appear that it 
should mingle with the chymous pulp, and then be brought into 
contact with the stomachic mucous membrane ; but, in the 
stomach, things do not exactly happen as was imagined a certain 
number of years ago. It must not be supposed that it is a mere 
cavity in which a mixture of substances takes place. By feeding 
rabbits during three days upon grass, then during one day upon 
carrots, CI. Bernard demonstrated that these last, recently intro- 
duced, formed a sort of cylinder, which occupied the central por- 
tion of the chymous pulp. 

Under such conditions it is difficult for the substance to come 
within reach of the mucous membrane in order to be absorbed ; 
it remains united with the alimentary pulp, and it can only be 
absorbed when these matters dissociate in the lesser intestines. 

Thus, as you see, great difficulties are offered to stomachic 
absorption, either when the stomach is empty or when it is filled 
with food. When the conditions I have just pointed out to you 
exist, one can understand how it is that the medicinal substances 
entrusted to the digestive duct are submitted to such actions, that 
their effects are enormously reduced and at times almost null, 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 7 5 

Think of what must take place in the case I have just men- 
tioned to you, in a substance like digitaline, which is liable to 
undergo chemical actions of every kind, and which will meet with 
acids and with oxygen (for we swallow air.) Do not substances 
like digitaline, which are eminently active when in a free Btate 
and not engaged in combinations, lose all their activity when 
they are consumed ? 

See what takes place as to phosphorus, a pre-eminently poison- 
ous substance when in a free state. This same phosphorus, when 
it meets in the stomach with a considerable quantity of air, can 
be transformed into phosphorous and phosphoric acids, so as to 
form a sort of intellectual lemonade, as the Germans call if, and 
this does not give rise to any of the accidents which are produced 
by the pure metalloid. 

Double decompositions also take place in the stomach, and 
these cause substances which are very active, to produce hardly 
any effects at all. For it is evident that if you take glyosidefi — 
digitaline, for example — and introduce it into a stomach contain- 
ing ferments capable of transforming those substances into 
sugar, on the one hand, and some other substance on the other, 
you will no longer have digitaline. This is the reason why, in 
a certain number of cases, no results whatever are obtained in a 
stomach that contains alimentary fragments. 

What I have said of the glycosides, I shall likewise say of the 
intermediary alkaloids between the glycosides and the typical 
alkaloids. There are, for example, a certain number of nitro- 
genized alkaloids which, nevertheless, when they are introduced 
into the economy, behave like the glycosides, that is, they become 
altered and are decomposed in such a way that in the secretions, 
particularly in the urine, they are no longer found. 

For example, there is in boxwood an alkaloid buxine, which 
possesses all the qualities of which I spoke a while ago, BO much 
so, that when we come to examine the urine, although the dose 
may have been increased to two grammes, nothing of it is found. 
There are others, like esculine, which is derived from the hark 
of the horse-chestnut tree, and even contain alkaloids, as 



76 PRINCIPLES AND METHODS OF THERAPEUTICS, 

nite, which are of such great instability that they become altered 
from the moment that they meet in the stomach with substances 
that are somewhat active. This is the reason why aconitine, 
which can be one of the most violent of poisons, can also show 
itself almost inert, according to the conditions in which the 
stomach happens to be. 

You see that all those phenomena have considerable import- 
ance. 

The practical rule to be deducted from what T have just said, 
is the following: organic substances must be administered while 
fasting, especially when they are easily alterable. The recom- 
mendation is absolute, when atropine and aconitine are concerned ; 
it is again nearly so in regard to the alkaloids from the poppy, 
although they are far more stable. But if active substances find 
a stomach laden with food, they will in great measure be altered. 
You must even avoid smelling dishes which you relish, avoid 
smelling the odors from the kitchens, avoid taking broth — all 
these things are to be shunned, because they are enough to call 
forth a very active secretion of gastric juice. 

We all know that the tempting of a dog by holding a 
piece of meat to his muzzle, will cause the gastric juice to gush 
forth, and if at the same time Vichy water is given to him, it 
will come as a real dew, a perfect rain. Consequently, adminis- 
ter those substances as remote as possible from meals, and away 
from the presence of food. On the contrary, we can give at 
meals, or just' before eating, those substances which offer greater 
resistance, such as the alkaloids from cinchona. 

Trousseau had observed that some stomachs became rebellious 
to quinine; it then occurred to him to give it at meal-time. 
Doubtless in this way it was better tolerated, but there is 
no doubt that it produced less notable effects, and that consid- 
erable quantities of quinine salts were required to obtain results — 
to obtain the effects of twenty-five or thirty centigrammes, not 
less than fifty were required. It is, especially desirable when 
metals are concerned, that the remedies should be administered 
at the same time with the food. 



AVENUES FOE THE INTRODUCTION OF MEDIO A M E NTS. 77 



CHAPTER VI. 

Avenues for the Introduction of Mediccvments— 
[Continued.] 

The Stomach — continued — Intolerance, trismus, esophageal spasm, cano 
vantage in introducing medicaments through the stomach; h biogenetic 
medicaments, alteratives, iron, arsenic. 

Lesser Intestine — The proper methods by which to retain its functions of ab- 
sorption, after introduction through the stomach; enveloping with tat and 
with gelatine; advantages of absorption in the intestinal tract. 

Larger Intestine — Its advantages, its facilities; medicinal injections; some 
inconveniences; proper methods for overcoming theni ; local act i I 
sensibility. 



Gentlemen : 

Besides the inconveniences connected with ine stomach, incon- 
veniences which I dwelt on at the last lesson, and which arc in- 
herent to the method of stomachic ingestion, there are also con- 
tingent inconveniences. For example, it is not rare that the 
gastric mucous membrane, either under the influence of the 
original disease or under that of repeated doses of an irritating 
substance, becomes very sensitive. This susceptibility opposes 
itself to the introduction of medicaments that are in the least 
irritating. Sulphate of quinine, in particular, can do Longer be 
tolerated, especially when introduced in high doses, as in torrid 
climates, where two grammes a day are a frequent dose. I nder 
such circumstances, one is placed between two dangers. On the 
one hand, that of the non-administering of the remedy ; on the 
other, the serious inconveniences which may result from it. 
gards thestomachal mucous membrane. There is, besides, ili« i diffi- 
culty offered by a certain number of rebellious subjects to the ad- 



78 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ministration of medicaments by way of the mouth, as children 
and women. Even at times an absolute impossibility exists, as 
with people who are affected with trismus, with esophagceal 
spasm, and with cancers, either of the mouth, tongue or pharynx. 

Notwithstanding all these disadvantages, the avenue of the 
stomach still remains the best ; it is that which must be most used, 
because it is easy, convenient and natural. To take medicaments 
by the mouth is doing something analogous to what we do when 
we introduce food, and the patient, requiring no lessons, leaves 
to the physician his liberty and preserves his own. 

Under our present conditions of life, these are advantages 
which will cause the oral method always to be most habit- 
ually practiced. Besides, it is the only one which is good for a 
certain number of medicaments. For example, for nourishing 
ones, for those which have been called analeptics, and which I 
have called histogenetics, that is capable of favoring the genesis 
of histological elements. Moreover, they are to be administered 
in such massive doses that it would be impossible to introduce 
them by the cutaneous way. I have only to mention cod liver 
oil, of which two, three, and four spoonfuls are taken daily. It 
is also evident that medicaments, like iron and manganese, could 
hardly be administered otherwise than by way of the stomach, 
inasmuch as they require either the liquids of the stomach or 
those of the digestive duct, in order to be absorbed and properly 
dissolved. 

Besides, I would add, that mixed with the chymous pulp, 
taking a place already among the peptones, they are half assimi- 
lated by the time they reach the circulation. 

There are also the alterative medicaments, which are eminently 
fitted for introduction into the stomachic cavity, and for being 
absorbed there. I have called these medicaments metatrophie, 
and this is the reason why : You are aware that formerly, apart 
from those remedies which produce such manifest effects that 
ordinary sick nurses could verify them, all others were called 
alteratives. Whenever the rudimentary physiology of the period 
prevented the mode of action of remedies from being understood, 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 70 

they were classed as alteratives; hence, the number of these was 
immense. Gradually, physiologists becoming enlightened by ob- 
servation and experience, the mechanism governing the action of 
a certain number of remedies was finally understood, so that by 
degrees alteratives were taken, and placed, some among the 
nervines, and others with the hypnotics. They were formed into 
classes, with regard to their therapeutic effects. In the end, after 
having constantly taken from the list of alteratives, there only 
remained a small number of substances to which the name might 
be applied. 

On the whole, they are medicaments acting in a slow manner 
upon the tissues. Among those substances, it is enough for me 
to mention gold, mercury and iodine. All these act upon 
nutrition, and this is the reason why I have named them meta- 
trophies. They are also substances which, in a certain number 
of cases, require to be hidden, as it were, in a more or Less con- 
siderable mass of adjuvants, by which their topical effects are 
neutralized, they requiring to be assisted in order to become 
absorbable. 

Those substances should likewise be introduced by the stomach. 
Not only through it, but especially when it is filled with aliment- 
ary matter. Thus, for example, iron, which acts as a modifier, 
in the sense I last mentioned, should be taken just before eating. 
The same is to be done with arsenical preparations because the 
topical inconveniences are diminished, and its dissolution is 
favored. 

In such a case, there is but one circumstance which should 
prevent the ingestion of the modifying medicament along with 
the food. It is when this substance exercises an injurious influ- 
ence upon the labor of digestion. 

An interesting chapter might be written on the action of medi- 
caments in the interior of the stomach, and the prima vi;c, the 
modifications to which they are exposed and their influence u\u>n 
digestion. 

I commenced this study upon phosphorus because I had 
observed that when giving it at the moment of taking food, 



80 PRINCIPLES AND METHODS OF THERAPEUTICS. 

there appeared, among a certain number of patients, troublesome 
phenomena of gastric dyspepsia, revealed by the indolence of 
the digestive duct, and often by eructations. I then conceived 
the idea of seeking for the influence of phosphorous upon pep- 
tic fermentation. I therefore caused a fistula to be made in 
a dog, and I tested the limpid and abundant gastric juice. 
I brought this high-grade juice in contact with cubes of meat 
contained in tubes. I also placed some upon other cubes, of 
equal quality and weight, but which had been dusted over 
with phosphide of zinc, which at that time was recommended as 
an energetic antagonist to paralysis. At the end of a certain 
number of hours, while the cubes which had not received any 
phosphide of zinc were softened throughout the whole of their 
brownish semi-transparent mass, the others had undergone no 
visible alteration whatever. Consequently, as you see, the pow- 
dered phosphide of zinc prevented peptic fermentation. Hence, 
you will understand, that it must also act in the same manner in 
the stomach. This is a circumstance to which attention should 
be given, but we are not well acquainted with the number of 
medicinal substances that hasten or retard digestive labor. 

I now come to the lesser intestine, which is the principal 
avenue of medicinal absorption. 

Active organs are always found there, and they give ample evi- 
dences of their absorbent propensities, whether the substances be 
dissolved in a fatty body or in an aqueous liquid. There still 
remains, however, principles acting the part of ferments — pancrea- 
tine, for example, which can, within a certain measure, modify the 
constitution of substances, and consequently modify their dynamic 
activity. But, as absorption is effected rapidly, there is also reason 
to believe that these alterations will not have time to take place. 

There would, therefore, be a very great advantage in. throwing 
the medicinal substance directly into the first portion of the 
intestine. There are, in fact, certain artifices by the aid of 
which substances introduced through the mouth may be made to 
reach the lesser intestine, not intact but less altered than they 
usually are. They are the following : 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 81 

The medicament may be introduced in combination with fatty 
matters, and if these fatty matters are but slightly fluid, or if they 
only become so at an elevated temperature, they pass through the 
stomach, retaining the principle with which they have been com- 
bined. 

We may also inclose the substance first in a gelatinous cap- 
sule, then cover it with a wax-like coating. In 1868, I n 
mended this process for the purpose of introducing bile into the 
digestive duct of patients who have not enough, and in whom it 
seems to be an indispensable element in accomplishing dig 
labor, or in cases where it was believed that bile could also be a 
useful agent in a certain number of nervous affections. If you 
have an object in causing bile to reach the interior of the intestine, 
it must be encapsuled and coated with some waxy matter, so tliat 
it will not disintegrate until it is in contact with the pancreatic 
juice. This advice has been followed by Mr. Mourrnt, who 
prepares a very useful and much better pancreatine than a num- 
ber of others which, in part, come to us from beyond the Rhine, 
and which are absolutely inert. 

There is also another process that has been used quite un- 
wittingly, but which nevertheless gives good results. 

When you introduce into the stomachic cavity an organized 
organic product, such as powdered cinchona or colocynth, you, in 
reality, introduce cells or fibres which contain the active princi- 
ple, and which only give it up by degrees, as it gradually wends 
its way in the digestive duct. Under these condition- a 
portion of the active substance escapes stomachic dissolution and 
is only absorbed by the intestine itself. 

The introduction by these processes of powdered colocynth, of 
drastics, like aloes, castor bean, jalap and gamboge, has built up 
the reputation of a large number of pills. I will not betray 
the secret, since certain manufacturers make a living by it, 
but I will tell you that certain pills owe their superiority Bolely 
to an envelope which enables them to enter the intestine 
without alteration. It may be said that the cells of the cellular 
tissue of colocynth travel the whole length of the intestine, and 

F 



82 PRINCIPLES AND METHODS OE THERAPEUTICS. 

only discharge themselves to advantage upon contact with ex- 
tended mucous surfaces. There results this double advantage — 
that no action takes place in the upper part of the digestive duct, 
no revolt of the stomach is produced, and the action is continued 
during a much longer time. 

I now have to speak of the rectum and of the colon. Physi- 
ology indicates, in advance, that the rectum and the S of the 
iliac are excellent tracts for absorption. 

How are the fseces modified in these last-mentioned portions of 
the digestive duct? This modification consists in the draining of 
the matters. Throughout the whole length of the lesser intestine 
they remain, so to say, fluid, hardly grumous or pasty ; they 
only become solid in the larger intestine, and their desiccation 
is completed in the iliac S of the colon, which lengthens the 
passage. It is consequently a surface constantly open for ab- 
sorption. 

What physiology indicates has been verified by the experience 
of centuries, and by more recent experimentation. We know 
of old, the value of clysters and of suppositories. More recently 
it has been noticed that alimentary substances can be intro- 
duced in this way, and can, to a certain measure, take the place 
of such substances introduced through the upper passages. 
Nitrogenized substances that are soluble, may thus be used, and 
even albumen, and especially substances that are more modified 
and approach nearer to selections from the animal kingdom. 
There are experiments which prove that by the aid of broth or 
of wine, it is possible to sustain the strength of subjects who 
have almost reached the stage of collapse. We often have occa- 
sion to use these methods in cases of oesophageal spasms, of tris- 
mus, of cancer of the tongue, and in incurable vomitings. There 
exist numerous observations on the subject by Bouisson, Aran 
Behieve, and others. 

This is not all. It may be said that, in a certain number of 
cases, this method is superior to all others. Dupuytren, Chomel, 
Orfila and Bouchardat have established that for a certain num- 
ber of remedies, absorption by way of the rectum is preferable 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 83 

to absorption through the stomach. Of course, it h on condi- 
tion that the remedy does not require acids in order to be 
solved. For example, a solution of opium, of extract of bella- 
donna, or of strychnine, is more readily absorbed through the 
rectum and the iliac S, than by the stomach and the ! 
intestine, because when substances are retained so long in the 
stomach, and their absorption prevented for such a length of 
time, when they do reach the lesser intestine they are often 
therapeutically and chemically changed. 

One cause of fermentation, however, exists : it is the presence 
of the epithelium, which acts the part of a ferment, as I have 
endeavored to prove that it did for urine. Urine, in its normal 
condition in the bladder, only ferments where living elements, 
at the moment they are detached, fall into the urinary reservoir, 
where they continue their functional action and act the same 
part as the histological elements which we call spores of rauoedi- 
nes — that is, veritable ferments. 

There has been, however, one discordant voice amid the con- 
cert of praise given in favor of the rectal method : it is the 
voice of my venerated colleague, Briquet, to whom we are 
indebted for an important monograph on cinchona. 1 1 1 
that quinine given in an injection is not so rapidly absorbed as by 
the stomach; the difference, however, is not enormous, for, at 
the expiration of half an hour, it shows itself in the urine. 

This fact is explained by a circumstance of a chemical nature. 
Sulphate of quinine is only slightly soluble by itself. To render 
it more so, acids have to be added to it, either can de rabel or else 
nitric acid. When a solution of bi-sulphate of quinine is intro- 
duced into the rectum, it meets there a certain quantity of mucus, 
which at times is considerable. (All mucus is alkaline, notwith- 
standing what may have been said to the contrary ; if it is acid, 
it is because fermentation has taken place.) This mucus which 
is alkaline, neutralizes a portion of the acid, by the aid of which 
the sulphate of quinine is held in solution. Hence, absorption 
takes place more slowly, but it is only necessary to introduce a 
greater proportion of acid to hasten it, care being taken to pro- 



84 PRINCIPLES AND METHODS OF THERAPEUTICS. 

tect the mucous membrane with some mucilaginous substance, like 
a decoction of marsh-mallow root. 

In conclusion, as you see, the rectal plan offers real advan- 
tages. There are also some drawbacks. These are of several 
kinds. Some are purely of a moral order. Among the French 
you will meet with persons who entertain serious prejudices 
against this mode of introduction. You must endeavor to over- 
come them. There is also this other drawback, that we cannot 
gain full command over the smooth fibres, so that when we in- 
troduce into the rectum an irritating substance, capable of exciting 
the contraction of the muscular membrane of the intestine, the 
substance is evacuated almost as soon as it is introduced. This 
is a serious drawback. I will tell you presently how it may be 
obviated. 

There are, moreover, difficulties resulting from certain lesions 
of the orifice, from hemorrhoidal tumors, from contractions of 
various kinds, from inflammations, and from fissures, which are, 
as you know, eminently painful. We have also to contend 
against the absence of substances in the rectum capable of dis- 
solving the medicaments when once introduced. We find there 
neither acids nor neutral salts, nor certain ferments, circum- 
stances which are less favorable than are presented in the upper 
portions of the digestive duct. Add to this, that purgatives 
which are active when given by the stomach, show less effect 
when introduced by the rectum. 

Aran has pointed out that twelve grammes of scammony resin 
or of .jalap, produce almost no results. But if it be dissolved in 
a certain quantity of alcohol, and kept in suspension by the aid 
of the yolk of an egg, it will produce purgative effects. Conse- 
quently, this is a slight inferiority, to which I shall attach no 
importance. There are ways of obviating all these little in- 
conveniences. For example, there is often a large quantity of 
mucus at the termination of the intestine. When you desire to 
introduce an important medicament, you must begin by clearing, 
by the aid of a copious injection, all that portion which is accessi- 
ble. Another danger is, that a revolt is possible, and that the 



AVENUES FOR THE INTRODUCTION OF MEDICAMENTS. 85 

rectum may exonerate itself after the remedy is introduced. In 
that case, you endeavor to render it tolerant, by means of a .slightly 
opiated injection. Or you introduce the least possible amount 
of vehicle, with the greatest^ possible quantity of energetic prin- 
ciple. In an extreme case you might introduce extract of bella- 
donna into the rectum, by the aid of the fingers, and after a 
certain time it would be in condition to retain the medical aeenl 
proposed. 

If these are inconveniences against which we can guard, there 
are also positive advantages. One is rapidity of absorption, as 
demonstrated by Demarquay's experiments. He made a 
number of tests to show the differences in the absorbing capaci- 
ties of the mucous membranes. He obtained his results by the 
use of iodide of potassium. This salt is highly dialytie, and is 
absorbed with the greatest facility, even by the stomach. It is, 
besides, one of the easiest drugs to detect, easier than you per- 
haps believe. When it is desirable to ascertain the pi 
iodine, in a combined state, in a liquid such as urine, we usually 
go to the trouble of having our druggist prepare a re-agent, and 
we take endless precautions. All this is useless. It is much 
more simple to immerse in the test-glass a sheet of paper, folded 
several times, and then pour a few drops of nitric acid <>n it. 
The paper assumes a blue color, the same as starch does. Con- 
sequently, these two qualities, great facility for being absorbed, 
and remarkable ease of detection, recommend iodide of potassium 
to the attention of experimenters. By its aid Demarqaay de- 
monstrated the greater rapidity of absorption by the rectum than 
by the stomach. Pirogoff and other surgeons have brought on 
anaesthesia by introducing chloroform by the rectum. 

Other circumstances may be mentioned in favor of this ave- 
nue. There are substances, disagreeable to the taste and smell, 
which can be introduced, and their use will spare the patient a 
certain amount of annoyance. 

There are also circumstances in which the stomach deolin 
receive- medicaments of great energy. All physicians from 
tropical climates who have prescribed sulphate of quinine in 



86 PRINCIPLES AND METHODS OF THERAPEUTICS. 

large doses will tell you how embarrassed they have been, when 
the stomach was in a state of revolt, in regard to continuing a 
treatment rendered necessary by the disease. In such case we 
can always procure the absorption of substances by the rectum, 
except, indeed, when we have to deal with dysenteries. 

I must add that when you have to deal with painful diseases 
of the organs contained in the pelvis, the uterus — ovaries, pros- 
tate gland, seminal vesicles and bladder — it is through the rec- 
tum that you should act. The reason for it is this : with the 
same dose of medicinal substance you thus produce a much 
greater effect upon the intra-pelvic organs, than through the 
stomach. The reason is plain. When I come to speak of the 
endermic method, I will show you that preference is to be given 
to the region nearest the seat of the disease. It is the same with 
the intra-pelvic organs ; when you introduce opium or extract of 
belladonna into the rectum, you, of course, invoke the aid of 
absorption, through the whole circulation, but you likewise act 
from proximate to proximate, by virtue of that sympathy of 
continuity and contiguity upon which I have already dwelt. 

You also act by way of nervous sympathy. That sympathy 
consists in this : the existence of nervous connection between two 
neighboring organs being granted, if you place one in a particu- 
lar condition, the other will imperceptibly be brought to a like 
state. This sympathy acts in two ways : one, which is known to 
you, is the response that is obtained from a deep-seated organ 
to a medicinal application at the periphery ; the other is but little 
known, but I have already called your attention to it. 

There are, as yet, unknown paths in anatomy and physiology, 
but clinical observers have noted them. I once called attention 
to them in the " Societe de Biologic." 

You will observe that when you have a pain and you cause 
friction at the point at which you feel it, you will experience a 
secondary painful sensation at a distant, but always at the same 
point; if the seat of the pain changes, that of this secondary 
pain will also change. You will note that there is a constant 
order in which these phenomena, which I call echoes of sensibility, 



AVENUES FOR THE INTRODUCTION OF KEDICAMES 

are evolved, and that they invariably manifest themselves at a 
point above that of the primitive pain. If the excitation takes 
place at the thigh, the painful point is at the abdomen ; if at de- 
base of the breast, then the echo will be in a region which is 
about that of the internal musculo-cutaneous nerve. No doubt 
what we here notice, where the sensory nerves are concerned, is 
also produced in that division of the nervous system belonging 
to organic life. 

Finally, there are circumstances in which administration by 
the rectum is the only plan possible. 

As long as I live, I shall never forget the following einn in- 
stance : Some years ago, there arrived in Paris a professor from 
Philadelphia, who consulted a certain number of physicians, 
myself included. Among other things, I prescribed for him 
extract of cinchona in doses of one gramme a day. lie did 
what laymen and even sometimes doctors do — he took at one 
dose what he guessed was a gramme of extract of cinchona. 
After a few minutes he experienced unutterable distress, and 
was seized with convulsive movements. His wife, an intelli- 
gent lady, concluded that he had been poisoned by strychnine. 
She went down to the druggist and inquired what had been 
given. They discovered that it was extract of opium. The 
man had taken one gramme of gummy extract of opium befon 
his breakfast. He fell into a state of deep coma, and was 
seized with incoercible vomiting. When I arrived he had been 
examined by several good physicians, among others by M 
Blondeau and Guerin. His condition was desperate, nothing 
could rouse him from the coma, and as soon as anything 
given him, even a little ice, he threw it up. Hi- pallor wa€ 
treme; it was believed he was about dying. I ordered thai an 
injection of one gramme of sulphate of quinine be given him, 
and, thanks to this antidote, he gradually recovered conscious- 
ness. The following day almost all traces of poisoning had dis- 
appeared. As you see in this case, that patient owed his life tn 
the possibility of introducing an energetic medicament by the 
rectum. 



88 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER VII. 

Avenues for the Introduction of Medicaments— 
[Continued.] 

Bladder — Weakness of absorbing faculty ; except in pathological cases. 

Urethra — The same. 

Preputial Mucous Membrane — Some local advantages. 

Vaginal Mucous Membrane — The same. 

Uterine Mucous Membrane — Dangers of this avenue ; uterine injections. 

Ocular Apparatus — Collyriums : atropine, daturine, duboisine, eserine, picro- 
toxin. 

Nasal Fossce and Pharynx. 
Eustachian Tube; Tympanic Cavity. 

Respiratory Organs — Gases and vapors, turpentine, sulphuretted hydrogen. 
Liquid Bodies — Kapidity of their absorption. 
Solid Bodies. 

Pulverulent Solid Bodies — Their introduction in the respiratory organs. — Pro- 
fessional diseases. 
Fumigations. — Inhalations. 



Gentlemen : 

We shall to-day continue the study of the avenues of into- 
duction,by considering the uro-genital apparatus, beginning with 
the bladder. 

For a long time the bladder was considered to offer an excel- 
lent absorbing surface, but precise experiments have demon- 
strated that this was an opinion which nothing justified. A 
priori, they might have guessed that the bladder was not 
intended for absorption ; indeed, if it absorbed, it would have 
been like the Danaides' seine, since it would thus have allowed 
the urine to escape, which incessantly flows into it. Fortunately, 
the bladder does not absorb, and the experiments of the older 



AVENUES FOE THE INTRODUCTION OF MEDICAMENTS. 89 

Segalas in 1824, and those of his son, confirm this proposition. 
Besides, within the last few years, experiments made with ex- 
treme care by a young "interne," of whom science has recently 
been deprived, Mr. E. Ailing, have proved that both in man 
and in animals the bladder does not absorb. 

There is, however, no doubt that in a certain number of 
cases, reliable observers have had occasion to note the e.\i- 
of general effects, due to the introduction of medicaments into 
the bladder. How is this to be explained ? Simply enough : 
in a healthy condition the bladder does not absorb, but an 
ulcerated bladder becomes a very active medium for absorption ; 
and this is precisely why Demarquay, who experimented on 
cases in which persons had diseases of the urinary organs, wit- 
nessed the most dissimilar facts with regard to absorption. 

At times it did not take place; no iodine could be traced ; then 
again, a little would be found at the end of from four to six 
hours; another time it would appear after thirty-five minutes. 
These differences are explained by the conditions in which the 
urinary reservoir happened to be. When absorption took plaee, 
it was because there were ulcerations ; when it failed, it was 
because the mucous membrane was healthy, and that there were 
no excoriations. Consequently, we cannot depend on the blad- 
der as a tract for medicinal absorption. In certain eases you 
may have results, but it will only be where the genital organs in 
general are impaired. 

The urethra is under the same con ditions : when in a healthy 
state, it absorbs very little — it is not intended for this purpose : 
but when inflamed, it becomes absorptive. Thus it is that in a 
certain number of cases when bougies coated with belladonna 
have been introduced, phenomena indicating a certain degree oi 
atropism have been observed — that is, dryness of the throat, 
thirst, with a more or less perceptible amount of mydriasis, 
Here there is not a real avenue for abrorption, only an accidenta] 
one. 

As much maybe said of the preputial mucous membrane, and 
yet there is an advantage in knowing some peculiarities it pos- 



90 PRINCIPLES AND METHODS OF THERAPEUTICS. 

sesses. It has been observed that solutions of iodide of potas- 
sium deposited between the glans and the mucous membrane 
have been absorbed rapidly, so that the iodine would appear in 
the urine, although every precaution had been taken to prevent 
its penetrating directly into the bladder. This has been noticed 
by careful observers, and in particular by Demarquay. It may 
be asked, of what advantage is this knowledge ? It is this : 
whenever it is possible to produce local sedative effects without 
causing the medicament to act upon the whole economy, you are 
to give preference to such a measure, because the very active 
remedies which we make use of in such circumstances, always 
have some disadvantages. For example, in certain nervous 
affections, such as neuralgias of the neck of the bladder, if the 
subject has a long prepuce, so that the sedative substance can be 
retained, you may find it advantageous to make use of this way 
in order to obtain an abatement of the general effects. 

The vaginal mucous membrane has been considered by some 
as capable of rapid absorption ; others have declared it cannot 
absorb at all. This discrepancy I explain as I did that about 
the bladder. In a healthy state, this mucous membrane absorbs 
but poorly, although perhaps rather better than the cystic mu- 
cous membrane; but when it is in a vascular condition, which is 
not rare in cases of vaginism and in leucorrhcea, where there is 
at all times a loss of epithelium, and in consequence more or less 
intense redness and even ulceration, then absorption takes place 
very well, so well, indeed, that serious accidents have been ob- 
served to follow the application of active agents. Thus, for ex- 
ample, Van Swieten's liquor having been introduced, absorption 
has taken place with such rapidity, that although this is not a 
means of producing phenomena of stomatitis, cases are on record 
in which acute mecurial effects were experienced. There are 
also cases in which a certain degree of atropism and of morphin- 
ism have been observed, consequent on the introduction of those 
substances into the vaginal cavity. Extract of belladonna in 
the vagina has often given rise to the phenomena I but now 
spoke of, that is, to a dryness of the throat and to thirst. Cases 



AVENUES FOR THE INTRODUCTION OF MEDIC a M I 

have even been mentioned in which it has been possible to intro- 
duce chloroform, under the form of vapors, and carbonic acid, 
and thus to determine more or less notable phenomena of 
anaesthesia. 

The facts about absorption by the genital organs in women — 
and I might extend it to the surfaces of the labia pudendi— 
should be remembered, because, while it is true that absorption 
only takes place with difficulty when they are unimpaired, ii 
is proven that it is easy when they are ulcerated. You know- 
how opinions differ on the subject of medicinal baths ; it lias 
been observed that they succeed better with women than with 
men ; it is evident that this difference is to be explained by the 
difference in the mucous membrane exposed to absorption. 

I shall now speak of the neck and the body of the uterus. 
If you refer to anatomy, you will see that here absorption must 
be easy, because the mucous membrane is of extreme vascularity ; 
its epithelium is in a constant state of desquamation, and conse- 
quently it is in the best conditions for absorption, especially when 
there is not too large a quantity of mucus secreted. This -ap- 
position has been confirmed in a great number of cases, and 
efforts have been made, not only to account for the reality of 
medicinal absorption by the uterine mucous membrane, but also 
for its rapidity. By proceeding in the customary way with 
iodide of potassium, (the experiments were made by I Vinar- 
quay,) it has been found that this agent is absorbed with such 
great rapidity, that it can be traced in the urine from a minute 
and a half to four minutes, at latest, after application. N 
theless, I do not advise you to make use of this way of intro- 
duction for medicaments. We are, at times, obliged to have 
recourse to topical applications to the neck; rarely should we 
venture as far as the uterine cavity, for troublesome accidents 
are sometimes produced when substances are introduced which 
are capable of producing irritating effects, and you will presently 
see that such effects are produced by substances which at first 
sight seem inoffensive. 

When injections have been introduced into the uterine cavity, 



92 PEINCIPLES AND METHODS OF THEEAPEUTICS. 

it has been noticed in a certain number of cases that they were 
followed almost instantaneously by vomiting and other symp- 
toms of peritonitis. 

No doubt by using precautions, by not forcing the injection 
too energetically, it is possible to avert accidents, but, after all, 
one is never certain to avoid all such risks. When you give an 
intra-uterine injection, and you induce serious accidents, are 
they necessarily due to the essentially irritating qualities of the 
substances introduced ? No ; you may introduce distilled water 
into the uterine cavity and produce most serious accidents. I 
have had frequent occasion to recall this observation upon one 
of Trousseau's patients. This patient had an affection of the 
peritoneum which communicated with the exterior. Trousseau 
treated him by mucilaginous injections, such as decoctions of 
marsh-mallow and of poppy. On one occasion the peritoneum 
having given signs of some slight irritation, the idea occurred to 
him to make injections with distilled water. The patient was 
almost immediately taken with extremely acute peritonitis. 
This might appear surprising, but it is not so, because irritants 
are not substances endowed with irritating qualities that are in- 
herent to their nature. 

An irritant is any substance that possesses properties greatly 
differing from those of the substances normally in contact with 
an organ. Hence, with still greater reason, an excitant is any 
substance whose qualities greatly differ from those of any organ. 

I shall give you an instance: The bladder, when we are 
warm, is sensitive to cold. You are warm ; you rise from bed, 
and are taken with a desire to urinate. You have been a long 
while exposed to cold. You approach the fire in winter, and 
there again you have a desire to urinate. To what is thfe owing ? 
To a change in the conditions under which the organism has, for 
a certain time, been placed. 

The same happens with the peritoneum. When you pour 
into the peritoneum a liquid, which, by its mild quality, resembles 
the peritoneal serosity, the peritoneum will tolerate it. But if 



AVENUES FOE THE INTRODUCTION OF MEDK A.MENTS. 

you introduce distilled water, that is, the oxide of that metalloid 
called hydrogen, intense irritation then takes place. That is 
what occurs when you put distilled water into the eye. It pro- 
duces a heating sensation. On the contrary, salt water, which is 
in every way similar to tears, produces no sensation whatever. 
I mention this so as to make you understand that you will not 
be safe against accidents, from the mere fact that you mat 
only of inoffensive substances in uterine injections. With how- 
much greater reason, then, if you introduce perchloride of iron 
into the uterus, as has been done in cases of fungous tun* 

It is a bad process. It is better to make use, as Mr. Richet 
does, of cauterization with nitrate of silver, because you are 
tain not to produce a distension, owing to which some of the 
liquid substance can penetrate into the interior of the tubes, and 
thus give rise to the most violent irritation, and, after a time, to 
real peritonitis. 

A great deal of discussion has been had upon the manner in 
which these phenomena take place. The thing which L have 
just explained seems to me the most probable. 

In certain cases inflammation of the uterus may be transmi 
to the tubes, and from there to the peritoneum. 

There is also another mode of action on the part of tin uterus, 
and that is over the sympathetic nervous system. It is a soli of 
sympathetic reflex action, comparable to that which you occasion- 
ally see developing itself, with such vehemence, when you mak 
use of a catheter. If you introduce a probe, when there is no 
material obstacle in the urethra, but where there i- a paralysis 
of the bladder, you may thereby give rise to an irritation which 
will manifest itself by an attack of fever having an intermittent 
type, comparable in every way to paludal fever. Ii is a sympa- 
thetic reaction. And it is by the same course that a case of deep- 
seated urethritis determines those phenomena that an- called 
blennorrhagic rheumatism. In this rheumatism the influence 
of the urethral affection upon the sympathetic system is BO well 
demonstrated, that when you test the urine of patients you de- 
velop a blue color in it the same as in that of subjects Buffering 



94 PRINCIPLES AND METHODS OF THERAPEUTICS. 

from abdominal diseases, an unquestionable proof of the reaction 
of the affection upon the abdominal sympathetic nervous system. 

I shall now say a few words upon the ocular apparatus. The 
cornea and conjunctiva are tracts in which absorption takes place 
rapidly. I speak of them especially because you will sometimes 
notice diffused effects from substances placed on the eye. When 
a mydriatic collyrium is used — for example, atropine — it is nothing 
very rare to obtain both a dilatation of the pupil on the side 
upon which the medicament has been applied, and also phenom- 
ena of dryness of the throat and thirst, and visual troubles in 
the healthy eye. In a certain number of cases, subjects have 
been seen laboring under that fantastic delirium which character- 
izes atropism when it assumes a rather serious form, thus prov- 
ing that absorption had taken place, not only by the conjunctiva 
and the cornea, but also by the lacrymal sac and the nasal fossse. 
When you desire to bring on mydriasis, and you make use of a 
rather strong atropine collyrium, you must be careful, and intro- 
duce but a small quantity at a time, and not pour it larga manu, 
as is often done. I would even add that a concentrated solution 
should not be prescribed. Very often the limit has been over- 
stepped. Thus, there are ophthalmologists who prescribe gr. 0.20 
for 20 grammes of water. This is a dose almost four times too 
strong. With gr. 0.05 you will obtain all the results you require. 

The same holds good with reference to daturine, which certain 
practitioners prefer. The same recommendation may also be 
made for the new alkaloid, duboisine. It acts like atropine, and 
although not as yet within the current domain of therapeutics, 
it will soon be. And likewise for eserine and picro toxin, which 
must never be used in too concentrated forms. 

The pharynx is also among the number of mucous membranes 
which can absorb. It has even been taxed with absorptions 
which really did not belong to it, as with certain phenomena of 
narcotism among inveterate snuff-takers. It was said that the 
tobacco which adhered there allowed its active principles to be 
absorbed, and that accidents might result therefrom. But with 
snuff-takers the tobacco is swallowed, and it is far more likely 
that absorption took place in the stomach. 



AVENUES FOR THE INTRODUCTION F MBDICAMEN1B. to 

The Eustachian tube and the tympanic cavity are also localities 

of absorption. Physicians who give their attention to diseases 
of these organs, have had oeeasion to witness the phenonn 
diffusion which are not infrequent with the substances employed 
especially with atropine. But they are not eligible tracts of* ab- 
sorption for medicaments. 

I now come to the consideration of the respiratory organs 
properly so called, for in speaking of the nasal Q | the 

pharynx, these are but a common vestibule; they are not the 
respiratory organs. The larynx, the trachea, the bronchia, 
finally the pulmonary alveoli, these are the real respiratory 
organs. This tract offers the greatest facility for medicinal ab- 
sorption, and the number of medicaments thus introduced ifi 
stantly increasing, not only because chemistry supplies us with 
very active volatile substances, but because we now have at our 
service the atomizing of liquids, which enables us to introduce 
not only volatile substances but even stable substances, which do 
not possess the faculty of being brought to a gaseous state. 

Let us first speak of gases and vapors. It is enough to In- 
acquainted with the physiology of respiration, in the essential 
portion of its history, to understand that gases may introduce 
themselves readily into the respiratory organ ; is there 

that the gaseous exchanges between the blood and the atmosphere 
take place. Experience constantly illustrates this. When, for 
example, you sleep in a recently painted room, your urine smells 
of violets. This will take place if you only remain two or three 
hours in such a room. Not only does absorption take place, but 
it is very rapid. 

This had been long ago observed by Magendie, who Bhowed 
that what is called "plomb" — that is, those terrible and almost 
always fatal accidents which befall those who descend into cess- 
pools — are due to the introduction of sulphuretted hyd 
into the blood. CI. Bernard, his pupil, has demonstrated why 
this intensity of action is so formidable as an effect of sulphur- 
etted hydrogen. He has shown that if sulphuretted hydi 
is nearly harmless when absorbed by the digestive membrane, a- 



96 PRINCIPLES AND METHODS OF THERAPEUTICS. 

is the case with sulphurous waters, it is because it can be immedi- 
ately exhaled by the lungs while it is being absorbed. On the con- 
trary, when it enters into combinations with the globules, the 
most serious accidents take place, because respiration is suddenly 
suspended, and it cannot be so, without all the vital phenomena 
being brought to a standstill. Another example of this instan- 
taneousness is in anaesthetics. At times, a few inhalations of 
chloroform suffice for narcotism to manifest itself. 

As to liquids, their absorption is also extremely active. One 
is surprised at the rapidity with which it takes place, and at the 
enormous quantities of liquids which can disappear when they 
are injected into the respiratory organs. Thus, 30 grammes of 
water have been introduced into a rabbit's lung ; 200 into that 
of a dog. 10 to 15 litres of water have been introduced into a 
horse's lung without any accident. This water is rapidly ab- 
sorbed. So great is this readiness, that Mr. Colin, of Alfort, 
has demonstrated that a constant current can be established ; 
that is, a liquid can be incessantly poured down a horse's trsechea 
into his lungs, and it is finally possible to kill him by the influ- 
ence of the ulterior modifications which this water determines in 
the blood and in the tissues, without a trace of the liquid remain- 
ing in the lungs when the animal dies. 

When solid substances are dissolved in the water which pene- 
trates into the respiratory organs, it is evident they must be 
absorbed along with it. Such experiments have been made, and 
the various substances used in them have been detected at the end 
of a very short time. Cases of poisoning by those active alka- 
loids whose characteristic phenomena cannot be mistaken, as 
strychnine or atropine, have likewise been observed. When 
atropine is introduced into the respiratory organs of an animal, 
phenomena of atropism immediately take place, with thirst and 
delirium, for animals have delirium, which is visible for those 
who know how to understand it. The same with strychnine. 
In the space of a few minutes we see tetanic phenomena super- 
vene, and the animal may die, if the quantity is sufficient. 
When substances like iodide of potassium are used, simply to 



AVEXUES FOR THE INTRODUCTION OF MEDICAMES 

demonstrate rapidity of circulation, it is found that at the end 
of three or four minutes this iodide, introduced by way of the 
bronchi, shows itself in the urine. 

If substances are in a solid state, in the form of dust, can 
they penetrate into the bronchial ramifications ? At first Bight this 
seems rather difficult, for if the way lay so widely open, we 
should be continually exposed to risks, and there would happen 
many more serious accidents than what we now see. 

Nevertheless, this introduction of dusts does take place, and 
the accidents to which those men who follow dangerous trades 
are exposed from this circumstance are known too long a time for 
any doubt to be possible. For example, wool-carders are subject 
to bronchitis and to phthisis, and when their autopsy is made, 
fragments of wool inspired by them are found in their longs. 
The same happens to the weavers of cotton, dyed with poisonous 
aniline colors. The particles of the cotton which find their 
way into the respiratory organs, give rise to accidents which arc 
well known to those persons who give their attention to hygienic 
questions. The same happens to those who break and 
stones. Bronze moulders are similarly exposed, and in 
Tardieu published a remarkable memoir, in which he called at- 
tention to serious accidents experienced by bronze smelters who 
make use of charcoal dust containing silica. 1 

One must remember, however, that these workmen, like others, 
blame everything upon their profession, and this, at tin 
warranted by the results of clinical observation, when, in point 
of fact, it is not the case. 

I remember a workman who had the appearance of being 
tuberculous, and who finally died in a state of phthisis, without 
tubercles, properly so called. He had, in the inferior porti 
the lungs, calculi, which appeared to be formed by the dusts he had 
breathed. I called attention to the fact that th 
and Mr. Berthelot and I analyzed them. We found thai these 
calculi were not formed by silica, but by earthy phosphafa 
carbonates. There was, however, one difficulty, to wit, that 

1 Tardieu. Annals of Public Hygiene and of Legal Med., 1864. 

G 



98 , PRINCIPLES AND METHODS OF THERAPEUTICS. 

earthy phosphates and carbonates are soluble in concentrated 
acetic acid, but these were not. This was due to the fact that they 
were coated with a viscid, albuminoid matter, which prevented 
them from being acted upon. When submitted first to heat, 
they then dissolved. You see that some reservations are to be 
made with regard to the frequency of such accidents 

Another case is on record which interests us more than these, 
and which proves the introduction of dusts in the respiratory 
organs. It is that of an apprentice in pharmacy, who could not 
pulverize ipecac, without being taken with an attack of asthma. 
This access of asthma was evidently connected with the intro- 
duction of the finely divided ipecac, dust, which forms very light 
clouds. Such instances illustrate the introduction of dusts into 
the respiratory organs. 

What becomes of these dusts? At times they form calculi, 
but they may also penetrate into the vessels and reach distant 
parts. The process is the same for them as for the particles of 
charcoal which are detained in the ganglions. With this question 
another is connected, which has created much sensation. It is 
that of the transmission of tubercle by contagion. Mr. Ville- 
min,l the author of this theory, believes that even a veil bought 
of a second-hand clothes dealer, may render a woman tubercu- 
lous. This is a field which we need not enter. I rest satis- 
fied for the present with having pointed out to you the introduc- 
tion of dusts into the respiratory organs, and I come to the 
applications that can be made of this fact in therapeutics. 

The respiratory organs have been utilized in many ways, to 
which different names have been given — fumigations, inhalations, 
inspirations. These organs have been used in the earliest periods 
of medicine, for even in those days, patients were made to breathe 
either the vapors of water alone or vapors laden with aromatic 
principles. They were also made to breathe vapors containing 
such substances as gum benzoin and frankincense. 

1 J. Villemin. Studies on Tuberculosis. 



RESPIRATOKY METHOD. INHALATIONS. FUMIGATIONS. 9i> 



CHAPTER VIII. 
Respiratory Method.— Inhalations.— Finn iga t to ns. 

Fumigations — Their origin. — Olfactory inhalations. The part which water 
performs in fumigations. — Humidity of the atmosphere. — Tetanus: 
emollient inhalations. — Inhalations of mineral waters: sulphurous in- 
halations. — Production of sulphurous waters. — The solphararise. 

Inhalations of Dry Vapors — Camphor, tar, essence of turpentine. — Eucalyptus, 
datura and belladonna cigarettes. — Nitre-paper cigarettes. — Inhalation of 
opium. 

Inhalations of Carbonic Acid, of nitrogen, of compressed air, of oxygen. 



Gentlemen : 

Scattered among the works of writers, we find evidence that 
from the most remote antiquity, vapors, and particularly the 
vapors of water, have been utilized in medicine. Vapor baths 
are nothing but confined places in which persons are submitted 
to a high temperature, and made to inhale the vapor of water. 
Fumigations with aromatic substances date back to the highest 
antiquity. The custom of burning incense in religious <'"rcm<>- 
nies has no other origin. 

Why the word "fumigation?" It is that which has remained 
the longest in use; it has only been replaced by anaesthesia. It 
is because the ancients did not make use of invisible vapors, ol 
gases properly so called, but of water vapors which presented a 
dense mist, and of dry vapors, which always give out a little 
smoke. That is the reason why those processes werecalled fumi- 
gations. This word is still applied to a number of methods by 
which medicinal substances can be introduced into the t 
organs; but, in general, the name is reserved for the external 
use of medicinal vapors. At times dry vapors are nsed in cer- 
tain aromatic baths. Arsenical fumigations are also employed, 



100 PRINCIPLES AND METHODS OF THERAPEUTICS. 

and others of sulphide of mercury. They are intended to act 
upon the skin. Watery fumigations are used on the pudendum 
in cases of hemorrhoids liable to become congested, and also 
upon young girls whose periods do not come on rightly. 

We must bestow special attention on those fumigations known 
by the name of " inhalations." As early as 1819, a physician 
by the name of Rapou published a lengthy work for the pur- 
pose of demonstrating the importance of this method; it has 
been called atmidatr-ic, and also eispinoic, that is, respiratory 
medication. It possesses considerable advantages. You know 
what importance it has acquired since the anaesthetic method 
came into use. 

I shall at present speak of the inhaling of humid and dry 
vapors, and to these last I shall join the inhaling of gas. 

I will not dwell upon those inhalations that are no more than 
olfactions. Persons on the point of fainting are made to inhale 
substances like ammonia or vinegar, which exercise a pungent 
action upon the Schneiderian membrane. But this is of little 
importance, as it is not a way by which medicaments can be 
introduced into the economy. Water vapor has been employed ; 
it is not, as a rule, used unmixed, yet, when patients are plunged 
into the atmosphere of a vapor bath, they inhale a great deal of 
water. In a great many circumstances it is the water especially 
that acts, far more than the substances that are added to it. It 
is not customary to cause simple water to be inhaled, yet there 
are circumstances in which you recommend processes that con- 
tribute to this inhalation. In warm countries, for example, in 
inter-tropical regions, where the humidity is such that the hydro- 
meter indicates 80° or 90°, when you attend persons who present 
considerable derangements of the nervous system, they are 
breathing watery vapor ; but in warm non-tropical regions, as in 
the south of Europe or of France, there are affections of the 
nervous system which are evidently increased by the dryness of 
the air. When I was at the grand hospital in Milan on my own 
account, having been wounded, I was placed in a ward that 
overlooked a small lake. The surgeons congratulated me upon 



RESPIRATORY METHOD. INHALATIONS. FUMIGATIONS, ldl 

my having been brought there, because in that ward there nev. r 
was any tetanus. So much so, that this observation having been 
made a longtime previous, the surgeons were in the habit of 
having transported into that ward those whose wounds being in 
the hands or the limbs were of a nature to induce tetanus. 
They even took the precaution to place under the beds earthen 
pans filled with water, which thus supplied more or less abund- 
ant vapors. This is a suggestion which may be useful, and 
which I have had occasion to recommend in the treatment of 
tetanus. 

I come now to the inhalations of water vapors laden with dif- 
ferent principles. Herbs possessing different qualities are often 
added to the water; at times these are emollient herbs, then 
again, more or less perfumed herbs, like linden; again, the 
water is laden with substances like belladonna, night-shade 
or datura. Such inhalations owe their qualities, in the first 
place, to the water — for I told you that this was their principal 
virtue — and secondly, to the substances added to the water. 

When emollient herbs are used, it is the water chiefly which 
acts; it is different, how r ever, in the case of linden, of 0] 
leaves, and of aromatic herbs, belonging to the umbelliferous 
and labiatae families — they are anti-spasmodics. Still more is 
this the case when belladonna, datura, or poppy arc concerned, 
since they contain principles capable of being volatilize d. 

In popular medicine there is often occasion to use inhalations 
of vapors charged with anodyne agents, and it would he wrong 
to neglect them. For example, when in presence of tracheo- 
bronchitis in the early stages, especially when the mucous Bur- 
faces are extremely parched, that is, when exaggerated secretion 
has not yet taken place, it may be of benefit to have the patient 
breathe water vapors laden with narcotic principles like those 
from belladonna. There are many circumstances in which this 
can also be useful; at the onset of acute bronchitis, oothii 
more soothing than such inhalations. They can be made very 
simply: hot water is poured into a basin over a certain quantity 



102 PRINCIPLES AND METHODS OF THERAPEUTICS. 

of aromatic herbs; by throwing a towel over the head a confined 
atmosphere is obtained in which the patient respires. 

Inhalations of watery vapors laden with mineral principles 
have an importance which is daily increasing as the use of min- 
eral waters is becoming better understood. Sulphurous waters, 
which disengage sulphuretted hydrogen, are, above all, those 
which have been used in this manner. The vapors of hydro- 
arseniated waters might also be inhaled, because arsenical waters 
are able to disengage arseniated hydrogen. When water remains 
for a long time in contact with organic substances, a 
smell is disengaged which recalls alliaceous orders ; I am well 
aware that the smell of garlic exists when arsenic burns, and 
consequently I must admit that it burns when in contact with 
the atmosphere. I have been told by many women, whose 
sense of smell is more delicate than ours, that they had often 
detected this alliaceous odor in places where arsenical waters 
had been kept. 

But, in general, sulphurous waters are those which are used 
for inhalations. These inhalations have been in use for cen- 
turies, but it is only since the year 1800, in a small bath in Ger- 
many, that they were regularly established. Since then, inhaling 
apartments have been established at many mineral springs. 

There is a certain historical and practical interest in having 
you here remark, that formerly there were a great many mineral 
waters which disengaged sulphuretted hydrogen, and which are 
mentioned in old books as sulphurous and hepatic waters, (the 
name liver of sulphur was given to sulphuret of potassium.) At 
the present day, they are no longer sulphurous. Is it that the 
geological conditions have changed? Not in the least. This 
result is due to an interesting circumstance. Before the waters 
were under control, when they were kept in their natural reser- 
voirs, in which considerable quantities of organic substances ex- 
isted, these waters became sulphurous. Thus it is that Loueche, 
which, probably, owed its first reputation to the fact that its 
waters were sulphurous, now no longer has waters exhaling the 
least smell of sulphur ; and this because they are under control, 



RESPIKATORY METHOD. INHALATIONS. FUMIG AT 1 1 

have been cleaned out, and in consequence, no longer und< ; 
any change. 

What, then, is the alteration giving rise to sulphuretted hydro- 
gen ? The explanation is now familiar, and Foutan, who class 
sulphurous waters under two categories — natural sulphurous 
waters, and accidental sulphurous waters — gives the process by 
which this sulphuration takes place. When organic substan 
are brought in contact with sulphates, particularly with sulphate 
of lime, this last is reduced and changed to sulphide of calcium, 
with a constant evolution of sulphuretted hydrogen. 

Such was the theory, which, however, offered some slight diffi- 
culties. The question was asked : How can substances be such 
powerful reducing agents when they are composed of but water 
and carbon, and leave behind carbon as a residuum? A novel 
and curious fact was, last year, introduced to science, completely 
changing, it was supposed, the physiognomy of this metamor- 
phosis. 

Mr. Plauchud, while studying the sulphurous waters of the 
south of France, conceived the idea of making a microscopic 
animation of the organized productions living in those wal 
He noticed that however carefully he washed the subetai 
which he desired to study, the next day they still exhaled the 
same sulphurous smell. He washed those substances with dis- 
tilled water, and then found that the smell had disappeared. It 
occurred to him there might be something contained in the ordi- 
nary waters which brought on this decomposition. Be at Length 
came to the conclusion that when those living organized sub- 
stances were placed in a solution of sulphate of lime, they instan- 
taneously determined the development of sulphuretted hydrog 
In other words, it is a fermentation, of which the fermenl is a 
species of alga?, which is found in all waters which undergo the 
sulphuretted modification, and which is to be found in the lit- 
tles of non-sulphurous mineral waters, when ^hese smell of rotten 
eggs. Thus, in all cases, when Spa water Bmells of sulphur it is 
because it contains the spores of those plant- which, having de- 
composed the sulphates, have given rise to sulphuretted hydro- 



104 PRINCIPLES AND METHODS OF THERAPEUTICS. 

gen. Mr. Plauchud has established a new theory on mineral 
waters, based upon this fact, and, according to him, it is always 
the presence of these algae which gives rise to sulphuretted 
hydrogen. 

One objection is to be made to* Plauchud's theory. It is that 
the sulphurous waters in the Pyrenees, well up at a temperature 
so high that it is incompatible with the development of what is 
called the sulfuraria ; it never exists in extremely hot waters, 
and yet these, as they well up, have the sulphurous smell. It 
is therefore impossible, in this case, to attribute the development 
of this smell to the sulfuraria. 

Some years ago, in 1863, I had the opportunity of making 
a few experiments which I consider very interesting. It was at 
Cauterets, and at a time when the spring was not yet artificially 
enclosed. I made thermometric and microscopic experiments to 
establish the relations existing between the vegetable species and 
the temperature. This was the condition of things at the time: 
At the moment of emergence, as the water flowed from a canal 
two kilometres in length, it had lost two or three degrees of its 
temperature; it did not register over -f- 50, and there was no 
trace of sulfuraria ; a little lower down its course there lived dif- 
ferent organisms; still further down, when the temperature had 
fallen to -\- 40° or -)- 42° Cent., the sulfuraria appeared. It 
was so evidently this temperature that was indispensable to the 
development of that botanical species known as leptomitus sul- 
furaria, that at one point near where a brook flowed in, causing 
a decrease of temperature of several degrees, the sulfuraria 
showed itself, while one or two metres above, the sulfuraria did 
not exist ; it was necessary that the temperature should fall to 
+ 40°. 

It is, therefore, evident that the formation of sulphuretted 
hydrogen cannot be attributed to the presence of the leptomitus 
sulfuraria, which only makes its appearance at the distance of 
several metres from the source of the mineral waters. This 
species is found in all sulphurous waters. It assumes a white 
appearance when it is incrustated with crystals of sulphur. It 



KESPIRATORY METHOD. INHALATIONS. FUMIGATIONS. 105 

cannot be made to account for the development of sulphn 
hydrogen, since it is as yet unborn, when sulphurous water 
already exists. 

But if all sulphurous waters do not owe their qualities to a 
peculiar fermentation of sulphates, under the influence of a 
botanical species, the fact is none the less an interesting one, and 
it holds true as regards accidental mineral waters. 

Sulphuretted waters containing soda, being more stable than 
the others, are preferable for the stomach; cold sulphuretted 
waters containing lime are especially good for inhalation-, be- 
cause they liberate more sulphuretted hydrogen. Thus em- 
ployed, these waters are soothing; they are excellent, when you 
have to deal with erethism of the respiratory organs, during tin- 
progress of chronic bronchial affections. They have also sub- 
stances held in suspension, which, although not volatile, arc car- 
ried along as vaporization takes place, especially if there is a 
disengagement of gas, for in that case a sort of ebullition i< pro- 
duced, which divides up the solid substance and project^ its par- 
ticles into the atmosphere. Thus it has been ascertained by 
chemical observations that fixed salts of the water used are con- 
tained in the atmosphere of the inhalation rooms of mineral 
water establishments, as at Royat, where the water- possess no 
other volatile substances but carbonic acid. I add, however, 
that these salts are found in very minute quantities, and that 
whenever water becomes finely divided there is a greal deal of 
vapor formed, which contains hardly any solid matter. 

I come to inhalations of dry vapors. They are of many kinds. 
Raspail caused camphor to be used under the form of inhalations 
in tubes — of glass or in a goose-quill. There was a time when 
every one used them. It may have some value, not tli.it it ren- 
ders one proof against cholera, as alleged, but it is soothing to 
the respiratory organs. 

Tar is in far more frequent use, and there are many persons 
upon whom its vapors produce very beneficial effects. A vase 
filled with tar is placed under the foot of the bed, or the steam 
of heated tar-water is inhaled, or, again, tarred papers may be 



106 PEINCIPLES AND METHODS OF THERAPEUTICS. 

employed. The latter are very handy, and I recommend them. 
They were invented by a druggist of Gers, who devoted his life 
to discovering the best tar preparations. He prepares a sort of 
cigar, which contains the aromatic principles of tar in such pro- 
portions that it is only necessary to inhale through it in order to 
feel one's self impregnated with tar. This is an excellent way 
of concealing one's necessity for using the remedy, and besides it 
admits of being used while walking. 

Inhalations of more or less analogous principles are well 
known : of essence of turpentine, or of the aromatic principles de- 
veloped by pine or eucalyptus branches. These are useful 
methods from which many patients derive benefit. Of course, 
these branches must not be in too great abundance. You can 
understand how this may be objectionable, for I have already 
told you that all aromatic vapors are anaesthetic, and that all 
hydro-carbons produce effects which are not identical but analo- 
gous to anaesthesia, so much so that the prolonged inhalation of 
essence of turpentine may give rise to accidents similar to those 
in a case of poisoning. 

There are localities in which these odors are supplied by 
nature. Thus Arcachon is greatly indebted to its pine forests, 
which are within easy reach of its visitors, where persons go to 
inhale the vapors of essence of turpentine. 

The smoke derived from the combustion of more or less nar- 
cotic plants is also used. You all know datura and belladonna 
cigarettes and others. It is a question whether these cigarettes 
are able to exhale active substances, or if such substances are not, 
perchance, instantaneously burnt. As regards datura or bella- 
donna cigarettes, their smoke does contain alkaloids capable of 
acting, because their alkaloids are volatile. I admit that a por- 
tion must be destroyed, but another portion must escape and be 
volatilized. In fact, enough is volatilized to give rise to tolerably 
marked phenomena. You are aware that this method is a favor- 
ite one in asthma. 

In similar cases use may be made of the gaseous products re- 
sulting from the combustion of nitrified paper. Tinder impreg- 



RESPIRATORY METHOD. INHALATIONS. FUMIGATIONS. 107 

nated with nitre might also be used. Nicolas Presi was the first 
to introduce it. This method is often successful in cases where 
the datura cigarettes fail. Hence, it is well to bear it in mind. 

But what is it that acts in this case, for it may well be . 
what possible effect can result from the burning of nitrate of 
potash ? Is it carbonic acid? Is it nitrous oxide, or is it os 
which is active? It is probable they each contribute a little, but 
it is the oxygen and the nitrous oxide which bring about the 
discontinuance of the attack. A variety of inhalations much 
more used, especially in certain regions of the East, are th 
opium. 

A French physician, Dr. Armand, had the idea of making 
use of this process. He has constructed a sort of cyliudi 
sembling a pipe, the bowl of which is of globular form and made 
of porous earth. In this bowl extract of opium is burnt, and 
the smoke is inhaled through the pipe. These inhalations may 
have their utility under several circumstances, owing to the rapidity 
w T ith which anaesthetic effects are produced. In casts of* intense 
dyspnoea, I have seen a sudden calm thus brought on. The in- 
halation of three or four puffs of this smoke, which contai 
Reveil has shown, almost all the alkaloids of opium, and 
especially a great deal of morphine, has been enough to produce 
sufficiently marked effects to bring on narcotizing results in the 
primae vise. I mention it to you that you may see that combustion 
does not destroy the alkaloids, and that even baneful things may 
serve a useful purpose, when employed in a proper mauner. 

I may here refer to the use of those more or less modified 
hydro-carbon vapors, which constitute anaesthetics, properly bo 
called, and with which nitrous oxide is to be joined. Then 
also, inhalations of gases, properly so called, such as carbonic 
acid gas, nitrogen, compressed air and oxygen. There arc a 
many springs which evolve such an enormous quantity <• 
and are continually bubbling, so much so, that they have the 
appearance of boiling. They generally owe this peculiarity t<> 
a constant escape of carbonic acid (as at Vichy and Vals.) A 
great number of foreign springs (Kissingeu, lor example,) are ^i' 



108 PRINCIPLES AND METHODS OF THERAPEUTICS. 

this class. They soothe certain cases of erethism of the respir- 
atory organs. But carbonic acid has not answered expectations. 
It is a bad anaesthetic. Besides, the external applications made 
with it have not all the value claimed for them. There are 
springs which appear as if they contained the same gas, but 
which only contain nitrogen, perhaps under the form of entozone. 
The illusion is such, that a manufacturer realized a heavy loss 
by believing he had secured carbonic acid, while it was only ni- 
trogen, of which he could make no use. The nitrogen disen- 
gaged by certain mineral waters is not useless, and there are 
patients who derive great benefit from breathing it. When a 
large quantity of nitrogen is liberated, it reduces the proportion 
of oxygen in the atmosphere, and consequently, the conditions 
of erethism which result from a more or less exaggerated com- 
bustion are benefited. 



AEKOTHERAPATHY. ATOMIZATION OF LIQUIDS. 



CHAPTER IX. 
Aer other apathy— Atomizatiot i of Liquids, 

Compressed Air — Its effect ; asthma. 

Rarified Air — Anaemia at high altitudes. 

Inhalations of Oxygen — Accumulation of oxygen in the blood. 

Ozone. 

On the Atomization of Liquids — Experiments. 



Gentlemex : 

I shall to-day address you on the subject of air, and the differ- 
ent modifications it can be made to undergo. It seems, at first 
sight, that air cannot enter into account among the Bubstaneea we 
inhale. But by modifying pressure — increasing or decreasing it 
— it is possible to modify the action of the air in various direc- 
tions. For example: Air under considerable pressures has often 
produced excellent results, in a certain number of affections, 
as asthma. These results are obtained when the patient is made 
to breathe air condensed by one or two atmospheres, as that 
supplied by the ordinary apparatus. 

The question arises to what are these favorable result- due? 
Is it to the condensation of oxygen or is it the mechanical action 
of pressure, so to say, forcing open the passages, through the 
membranes of the respiratory apparatus, the pulmonary \ 
and the capillary vessels ? 

It is probable that these two circumstances have each an influ- 
ence, but an influence which seems to be unequal. The tendency 
is more and more towards giving the preponderance t-» tin ; 
ure, and the interesting experiments made by Mr. Paul Berl 
demonstrate, in a telling manner, the influence of high 



110 PRINCIPLES AND METHODS OF THERAPEUTICS. 

either to modify respiration and the nervous system, or to pro- 
duce more or less dangerous effects, comparable to those of light- 
ning stroke. In these cases it is not the composition of the air, 
but the pressure exercised by it which produces the effects we 
witness. It is extremely probable, that even in air compressed 
under one or two atmospheres, it is mainly pressure which causes 
the respiratory modifications. In the absence of a rigorous 
demonstration, I quote an analogy : In the establishments in 
the streets de Malesherbes and Chateaudun, where baths of com- 
pressed air are given, you may witness real cures of asthmatic 
attacks. This disease does not yield to oxygen ; it is not its 
greater or less proportion which can dispel an attack of asthma, 
for asthmatics do not require an increase of oxygen, and, as I 
often say, they are only well when in a second-hand atmosphere. 
Hence, there are no asthmatics in Paris. Those from the prov- 
inces are in a state of beatitude when they arrive there, and are 
distressed when they again breath the country air, especially the 
air on the sea shore, that of uplands, and that from the neigh- 
borhood of extensive forests. This is so true, that it is only 
necessary to have such persons return to the interior of Paris in 
order to prevent the recurrence of their attacks. Such being the 
case, it is not the greater quantity of oxygen in baths of com- 
pressed air which can be the cause of relief. It is more likely 
that the attacks yield to the pressure itself. 

I shall only say a word on the subject of rarified air. Mr. 
Jourdanet, a distinguished scientist, who for a long time has 
resided in the high table-lands of Mexico, has ascribed very 
great importance to rarified air.l He has seen it produce anae- 
mia, and he has advised its use as a means against the tendency 
to tubercles. Having remarked that although Mexicans have a 
tendency to become anaemics, they are less liable to be tuberculous, 
he brought these two facts together,- and established a sort of 
antagonism between anaemia and tuberculosis. His conclusion 

1 Jourdanet, Mexico and Tropical America Climates, Hygiene, Diseases. 
Paris, 1864. Karified Air in its Eelations to Man in Health and Disease. 
Paris, 1862. 



AEROTHERAPATHY. ATOMIZATION OF LIQUIDS. Ill 

is, that it cannot fail to be of benefit to those Buffering from 
tubercles to breathe the air on high table -lands. 

It is very possible that under the conditions in which the 
high table-lands of Mexico are, there may be no sufferers from 
tubercles there. With regard to anaemia, I recall a conversation 
which I had with a distinguished personage who has lived on the 
high table-land above Quito, at an altitude of 4200 metres. 
While there he had to put up with a great many privations, 
but this did not prevent him from taking daily observations, 
the results of which he sent to the Paris Academy of Sci< 
I questioned him for the purpose of learning if at Anti/ana 
and at Quito (an altitude of 2200 metres) there were habitual 
ansemics. He replied that, on the contrary, the population was 
in splendid physical condition, and that the inhabitants were 
very vigorous. You see that there are reservations to be made 
as to the influence of altitude upon the development of ansemia. 
Hence it were presumption at present to infer a sort of antago- 
nism between anaemia and tuberculosis. 

Inhalations of oxygen have long been in use. At the 
end of the last century, following Fourcrov's example, they 
were used against asthma. This malady chiefly presenting diffi- 
culty of breathing, seemed to call for either condensed air or 
pure oxygen, since the purpose was to supply air in excess to the 
patient. In Laennec's time, oxygen was tried against asthma, 
but without success. In other cases where better results were 
obtained, it is evident they had not to contend against asthma, but 
against real dyspnoea, or, if you prefer, against asthma sympto- 
matic of a lesion of the heart, or of other affections of the 
thoracic organs. Oxygen does not suit asthmatics, and, for my 
part, I have never seen it successfully used against asthma, prop- 
erly so called. 

After the negative results obtained by Laennec, oxygen inhala- 
tions fell into disuse. Afterwards, the experiments made by 
Regnault and Keiset have again called attention to this gas, and 
it has once more come into favor. Besides, mannfacturers and 
chemists have supplied apparatus allowing inhalations to be 



112 PRINCIPLES AND METHODS OF THERAPEUTICS. 

made at home. As you are aware, at the present day large bal- 
loons are constructed of impervious vulcanized rubber, which are 
capable of containing 10, 20, 30, and 100 litres. These balloons 
are filled with oxygen obtained as pure as possible, but not en- 
tirely so, since it always contains a small quantity of carbonic 
acid. To the balloon provided with its tube, Mr. Limousin now 
adapts a double-necked wash bottle, through which the oxygen 
passes when it is inhaled, and in which it is divested of its car- 
bonic acid. Now that we have a portable apparatus which holds 
oxygen gas very safely, and which supplies it in a pure state, we 
may make use of it in many circumstances, and obtain very 
good results. It is valuable, for instance, in cases of dyspnoea, 
symptomatic of a lesion of the heart, and when the patient is in 
a state of cyanosis and almost pulseless. Often after the patients 
have breathed a few litres of it, (and, if needs be, they might 
exhaust one of those flasks) you see them greatly relieved for a 
time. But what you thus obtain in a very restricted manner, 
with oxygen inhaled in a difficult way, (the patient having to 
hold the tube in his mouth,) you would obtain far more readily 
were it possible to breath free oxygen as one does a current of 
air. 

Once in my life it has been in my power thus to cause the 
breathing of free oxygen coming in considerable quantities. 
Thanks to the liberality of the Oxyhydric Gas Company, gaso- 
meters such as those which contain portable gas, were placed at my 
disposal. I thus had under a pressure of one and a half atmospheres, 
a considerable quantity of nearly pure oxygen containing only a 
very little carbonic acid. The gasometer being placed in the 
yard at Beaujon, a long tube bringing the gas into my wards, I 
could have a patient affected with heart disease seated upon a 
chair, and the current of oxygen discharged in front of him. 
Well, persons who were the whole day suffocating, who were in 
a state of cyanosis, chilled, and with a feeble pulse, would walk 
away unaided after they had remained a short time in that 
atmosphere of pure oxygen, and they would remain, at times, five 
or six hours without suffocating. The suffocation would then 



AEROTHERAPATHY. ATOMIZATIOX OF LIQUIDS. 1 1 3 

gradually return, and they would fall back into their previous 
condition. Of course it was not the provision of oxygen they 
carried away with them which was the cause of this long ame- 
lioration; their nervous system had undergone a modification. 

I just said they carried away with them a provision of oxygen ; 
here is the proof of it : while under the immediate influence of 
the gas, there was neither elevation of temperature nor stimula- 
tion of the respiratory apparatus, nor any increased rapidity of 
the pulse,, but rather a diminution in its beats and increase of 
volume. On one occasion, while this kind of sedation of the 
circulating system was taking place, one of my pupils stopped 
his breathing, and found he could hold his breath for a consid- 
erable time. Each of us then did the same, and we undertook 
to measure the difference which there was according as oi 
had been inhaled or not. Here are some figures : one of my 
pupils at that time, Dr. Ayello, who, under ordinary circum- 
stances could only 'hold his breath from 30 to 35 seconds, after 
breathing oxygen held it for 90 seconds. Another, Dr. Powell, 
who could only hold his breath during 45 seconds, held it dur- 
ing 110 — a little more and it would have been two minut 
give you these figures, because the proportion always stood in 
'about the same degree, and each of us always experienced the same 
effect. I add, that those who could hold their breath the longest 
time, were those whose blood was less rich, whose blood con- 
tained the least number of globules. What does that prove.' 
It proves that inhaled oxygen, oxygen pure and free, circulating 
like air around the subjects, did not produce any more combus- 
tion than air itself. It proves, again, that if this oxygen did not 
burn any more than air within the same time, that it was I 
theless there in the form of a reserve, and that it enabled the 
breathing to remain suspended. Another inference from these 
experiments is, that whatever be the quantity of combustibl 
introduced into respiration, this gas will only burn in proportion 
to the number of the globules of the blood. If there are many, 
the proportion of inhaled oxygen is sooner exhausted ; if there 
are but few, the action progresses more slowly ; it is possible to 

H 



114 PRINCIPLES AND METHODS OF THERAPEUTICS. 

hold one's breath for a longer time than in the first case, and 
without suffering. 

These interesting facts have also been observed by Mr. Paul 
Bert, who calls attention to them and others in every way 
similar, 1 although ignorant of what I had written on the sub- 
ject. This adds further testimony in favor of the interpretation 
I have just given you. 

I have a word to say about ozone. Both useful and harmful 
qualities are freely attributed to it. I must say that we have no 
proof either of its usefulness or of its inocuousness. For my 
part, from what I have seen in Thenard's laboratory, I am con- 
vinced that it is dangerous. People always have as an ideal, the 
breathing of ozone; and every one believes that if the air of 
forests is so very healthy, it is due to ozone. I do not place my- 
self in antagonism to sturdy beliefs — rather, I accept them ; but 
I believe that ozone can only render really useful services on 
condition that it exists in very weak proportions in the air. If 
it happens to be present in any considerable quantity, it will 
bring on accidents, real intoxications, characterized by extraor- 
dinary intensity and rapidity. I remember on one occasion, at 
the suggestion of P. Thenard, I took repeated inhalations from 
a flask which contained pure ozone. I noticed nothing at first, 
but after a few moments I was seized with vertigo. Both he and 
his father, after having made the same experiment, experienced 
similar and most unpleasant effects. Imagine the sensations 
which would be produced by the odors of flowers in a close 
room, and this carried to their greatest intensity, and you will 
form some idea of the effects produced by ozone. If it is ever 
introduced into therapeutics, many precautions will have to be 
taken in its exhibition. 

I am now through with the subject of inhalations of vapors, 
or gas. But there would evidently be great advantage in intro- 
ducing through the respiratory organs non-volatile substances. 
I do not speak of pulverulent substances, but of those which can 
be held in suspension by water. Remember the absorptive 

*P. Bert. Barometric Pressure. Paris, 1878. 



AEROTHERAPATHY. ATOMIZATION OF LT^rms. 1 j •", 

power of the respiratory tract, and you will understand what 
advantages there are in introducing non-volatile substances 
through it. 

The atomizing method seems to supply this want, but the 
question presents itself: Is it necessary to atomize a liquid in 
order to introduce into the respiratory organs the fixed principles 
which it may hold in solution? Do we not know how difficult 
it is to obtain distilled water; that it often requires three distil- 
lations before it is completely pure? Nothing is more difficult 
than to free it from chloride of sodium. It has been shown that 
if Vichy water is projected on the surface of a red-hot shovel, 
and the steam is condensed, it contains sesqui-carbonate of 
and all the other salts of Vichy water. It has also been observed 
that on all the surfaces of inhaling halls in all watering places, 
the soluble, but non-volatile, substances contained in the differ- 
ent waters can be detected. It would, therefore, at firsl 
appear that all that was necessary would be to volatilize any kind 
of water, and that its vapor would contain all the princip 
held in solution. This is, in a measure, true, but Thenard has 
shown that it is when the distilling operation has been badly con- 
ducted — when bubbles break on the surface of the liquid, and 
a certain quantity of water passes over, that then the water in 
the receiver is found to contain fixed mineral substances; but 
on the contrary, when the operation is well conducted, <i\<d sub- 
stances do not pass over during distillation. This show 
that you cannot depend upon simple volatilization in order to 
cause solid and fixed principles to penetrate, in any eonsidi 
quantities, into the respiratory organs. 

This desideratum of therapeutic- is sought to be obtained by 
the atomizing process invented by Sales Girons, ! and lor (he ap- 
plication of which the director of the mineral waters at Pierre- 
fonds has had an instrument constructed like a pump-barrel. 

1 Sales Girons. Physiological Theory of the Penetration to the 
Eespiratory Organs. (Bull.de I'Acad. de Mc<L, Dec LOth, 1861. NTen Pul- 
verizer of Liquids. (Bull, de V Acad, de Mid., Feb. 7th, L» LXX p. 

367.) 



116 PRINCIPLES AND METHODS OF THERAPEUTICS. 

throwing a jet which forms a more or less fine spray. These 
apparatuses have been greatly modified, as regards the motive 
power and the various mechanical parts, and such improvements 
have given rise to remarkable modifications in the qualities of 
the liquid obtained. At first, visible and tangible droplets were 
ejected. By holding one's hand in front of the apparatus, one 
could feel a manifest percussion, and brilliant drops were seen, 
which, when struck by the rays of the sun, gave the colors of the 
spectrum. Gradually as the apparatus was improved, it has at 
last been brought to create a kind of mist or haze — a sort of 
cloud — which reminds one of what may be seen, before sun- 
rise, over swampy regions. That is exactly what you may ob- 
serve with the perfected apparatus of the present day. It may 
be said that they obtain a real nebulosity, or haziness, a sort of 
vesicular vapor. I insist upon the comparison, not that I be- 
lieve that the vapors, of which I just now spoke, and which 
constitute the clouds, are vesicular: — they are called vesicular 
vapors — but I may refer to Mr. Jamin, who, while he does not 
believe that they are vesicular, nevertheless assimilates the ap- 
pearance of mists to so-called vesicular vapors. For my part, I 
represent them to my mind as constituted by minute molecules, 
of which each is the centre of a particular little system. That is 
what you see in the case of solid dusts, which, notwithstanding 
their density, when they are of extreme tenuity, can be carried 
very far ; as, for example, the dust from volcanoes. You know 
that the fine sands of the Sahara desert cross the Mediterranean 
sea with such ease that when the simoon blows, the city of Mar- 
seilles is covered with a peculiar dust from remote Africa. These 
dusts, although of very dense bodies, are excessively light, owing 
to the reason I have just given. 

After this condition of haziness and excessive division of water 
has been obtained, the mist then presents qualities differing from 
those possessed by the coarse atomizations resulting from the 
first instruments used. The small visible droplets can only be 
made to penetrate a short distance into the interior of a glass 
tube, or they can be seen adhering to the lower segment of the 



AEROTHERAPATHY. ATOMIZATION OF LIQUIDS. 117 

tube. On the contrary, with a mist, you can see the cloud pene- 
trating a very long tube, winding its way through it and issuing 
from a minute orifice, at its other end, just as the smoke or 
gases of combustion would do. 

The following experiment, made within the last few years by 
Sales Girons, is conclusive: He imitated the trachea and the 
bronchi by means of a long glass tube which bifurcated at a cer- 
tain height, each branch ending by extremities drawn out over a 
lamp. He then introduced atomized water, under the form of a 
mist. This penetrated into the tube, rose within it and issued 
from the small orifices, in the same way as visible smoke 
would have done. You readily see that under these conditions 
there is no reason why air laden with this mist should not con- 
vey it along into the depths of the respiratory organs. It is 
probable, that by placing one's self under analogous condition, 
the mist would behave in the same manner as a gas. Experi- 
ments in support of this were made, before the highly improved 
apparatus I told you of a while ago had been invented, by ( te- 
sian Henry upon rabbits. He made them breathe an atomised 
solution of ferric sulphate, then would kill the animal, and, 
laying open the respiratory organs, would bring in contact with 
the different regions a rod dipped in tannin. Tannin and sul- 
phate of iron form ink, and such ink could be produced in the 
deepest recesses of the bronchial ramifications. These « iperi- 
ments were repeated by Gratiolet, who verified the Bame state- 
ment. They were made anew by Demarquay,! who 
great ardor for the study of experimental science. I [e lib 
made use of ferric chloride and of tannin. He proceeded in the 
following way: He caused a rabbit to breathe an atomised solu- 
tion of perchloride of iron, holding it at 20 to 30 m 
the apparatus for a minute, and then allowed it to rest He 
would thus replace it several times, and finally kill it. 
with a rod dipped in cyanide of potassium, he verified that the 
salt of iron had penetrated throughout the Lung. He found it 
even in the pulmonary parenchyma. 

1 Deraarquay. On the Penetration of Atomised Liquids into the Beep 

Organs. (Bull, de V Academic de Mid* ■ e, Sept. 24th, 1 - 



118 PKINCIPLES AND METHODS OF THERAPEUTICS 

But here a precaution is to be observed, similar to that recom- 
mended by Claude Bernard, when the point was to ascertain the 
presence of ferro-cyanide of potassium in the stomach. A cer- 
tain proportion of acid is to be added to the pulmonary paren- 
chyma. For although the ferric chloride is colored, it is not 
present in sufficient quantities to be easily detected. I add that 
the lung is so thoroughly reached by atomization, that in some 
cases more or less serious inflammations are developed. 

These experiments upon animals are conclusive. There is 
one which will appear to you even more so. It was performed 
in presence of a commission of which Poggiale 1 and Gobley 
were members. It took place at the Beaujon hospital, upon a 
nurse, who, after having undergone tracheotomy, had remained 
subject to considerable dyspnoea. She had paralysis of the vocal 
ligaments, especially of those on the left side, and on this account 
her canula had not been taken from her. An apparatus was ad- 
justed so as to close the orifice of the trachea, and she was caused 
to inhale the atomized vapors of a tannin solution. When the 
inhalation appeared to have been continued long enough, she 
was loosened from the apparatus, and then it was found that when 
the interior of the trachea was touched with ferric chloride, ink 
was produced. This is an experiment against which nothing can 
be objected. It is therefore evident that atomized solutions — 
and I add those especially that are in the form of a mist — pene- 
trate not only into the upper portions of the respiratory organs, 
but also as far as the pulmonary alveoli. This fact being de- 
monstrated, we can advance to some other inquiries. Does much 
substance penetrate ? Yes ; and enough, under certain circum- 
stances, to lead to remarkable results. 

But I must here pause to say a few words upon the modifica- 
tions which the liquids used undergo, either in their chemical 
composition or in their temperature, because from this knowledge 
there will result indications for therapeutics. 

When the proportion of solid principles originally in solution, 

1 Poggiale. On the Atomizing of Mineral and Medicamental Waters. 
{Bull, de UAcademie de Medicine, Jan., 1862, tome XXVII., pp. 267, 799, 815.) 



A EROTHER APATHY. ATOMIZATION OF LIQUIDS. 119 

or in the mineral water is small, these same substances 
found in about the same proportions in the atomized water. I f 
it is the water from Enghien or from Pierrefonds that is 
there will be present the whole of the sulphide of calcium, the 
carbonate of lime, the chloride of calcium and the sulphate*) of 
lime and of magnesia; in fact, all the fixed salts remain in 1 1 1 < * 
water when reduced to a mist, and in the same proportions. 
That is the result of Ossian Henry's experiments, confirmed by 
those of Poggiale. An attempt has also been made to ascertain 
the amount of volatile principles which these same water* 
and it has been found that in sulphurous waters containing lime, 
a little more than half of the gas escape*. But this fact is of do 
importance, from a therapeutic point of view, because sulphuret- 
ted hydrogen is always present in abundance. 



120 PKINCTPLES AND METHODS OF THERAPEUTICS. 



CHAPTER X. 
Atomization of Liquids. 

Chemical Alterations of Atomized Mineral Waters. 

Physiological Action of Atomized Douches — Percussion, temperature, chemical 

composition, precautions to be taken ; atomizing of sulphate of quinine 

solutions. 
Atomvzation in Ocular and Uterine Cases. 
Aqua-puncture. 



Gentlemen: 

Let us now see what are the chemical alterations which atom- 
ized mineral waters may undergo. It t has been thought that 
they must lose oxygen to a high degree. In fact, Ossian Henry 
has observed, that in atomizing halls, the proportion of oxygen 
was only represented by 19 5/ 100 per 100, instead of 21. However, 
this observation has not all the value claimed for it, because it 
has often been noticed that in halls where there are a great 
many persons, there is always a lack of oxygen. In order to 
have the normal proportion of this gas in the air, it is not indis- 
pensable that one should be in open country, since we know that 
in the experiments made at the Sorbonne, 20 84 /ioo °f oxygen 
and 79 L6 /ioo of nitrogen have been found, but when one is within 
an entirely confined place, there is always a diminution in the 
oxygen. Nevertheless, we should not conclude from this that 
combustible substances which are in solution in mineral waters, 
do not undergo de-oxygenation when atomized. This influence 
exists. It is manifest around sulphurous waters, and especially 
those degenerated sulphurous waters which contain hyposulphites 
and large proportions of sulohates. These waters owe that 



# 

ATOMIZATION OF LIQUIDS. 121 

change precisely to the combustive influence of oxygen, which 
changes the sulphur into hyposulphurous and hyposulphurie 

I now pass to the physiological effects of these atomized 
douches. We first distinguish topical effects, themselves con- 
nected, on the one hand, with the physical conditions, and on 
the other with the chemical nature of the substance or the -lib- 
stances held in solution by the water. 

The physical effects relate mainly to percussion and temperature. 
When one receives a douche, atomized by an imperfect apparatus, 
in which the orifice is not very fine, and when the pressure is 
small, the discharge is in the form of drops, which fall to the 
floor. When this jet is brought in contact with the interior of 
the throat, and these visible drops come to strike the wall of the 
pharynx and the entrance to the respiratory organs, all patients 
complain of a peculiar pricking sensation, which can only be 
accounted for by the shock from the droplets, which si ill retain 
a considerable momentum. At the same time a notable excita- 
tion is produced, which may give rise to a sort of dyspnoea, to 
which one finally becomes accustomed, but which often manifests 
itself at the start by a slight spasm. A grasping sensation is ex- 
perienced at the throat, a contraction of all the organ- takes place, 
so much so, that at times it becomes necessary to suspend the 
action of the water. I must add that when the water is in a 
nebulous condition, this phenomenon does not take place. 

Whatever is the mode of atomizing, however -real the tenuity 
of the drops, the influence of temperature is always present. 1 P 
one approaches very near to the jet, the initial temperature wall 
make itself be felt with great intensity. Suppose you bave v.-i -y 
cold water, like the one I spoke of a while ago, Bay, at + 4°, or 
else very hot water, about + 40°, these will be the temperatures 
possessed by the atomized jet. 

This indicates that it is indispensable to hold the instrument 
far enough from the entrance of the mouth, thai is, al »> ; 10, or 
at m 15, at the most. It is here that the condition of initial 
temperature interposes itself. If you place yourself yerj Far 
from the jet, the water, although cold, may have acquired the 



122 PRINCIPLES AND METHODS OF THERAPEUTICS. 

temperature of the surrounding atmosphere ; but then, because 
of the distance, you lose a portion of the water. If, on the con- 
trary, you use water at -f- 40°,'and you place yourself at a distance 
m 10 or m 15, you have water at + 30° or + 32°, a temperature 
which is very appropriate. For the best effects, one should feel 
neither warmth nor chill, since warmth might produce hyper- 
emia of the surfaces touched; and one should not feel the 
water cold, otherwise all the effects of a local douche are ob- 
tained. In the same way that after an external douche you 
notice vascular contraction, followed immediately by reactionary 
phenomena, as redness and elevation of temperature, so you can 
obtain by means of a cold douche in the interior of the mucous 
cavities, these first effects of contraction followed by excitation, 
which may extend beyond the proper limit. You can thus un- 
derstand why it is indispensable to have water at a definite, tem- 
perature; it must not be less than -(-22° nor over -(-32°. 

When these conditions are overlooked, patients suffering from 
simple chronic diseases, or from those of a tuberculous nature, 
are exposed to contracting dangerous colds. 

There is a third condition to which you must pay particular 
attention, that is, the chemical nature of the substance held in 
solution by the water. If, for example, you prescribe atomized 
douches of astringent solutions, like those of tannin, of iodine, 
or of nitrate of silver, you must take infinite precautions that those 
substances, which are very active even when they are diluted, 
do not penetrate too deeply, otherwise irritations of extreme 
intensity may be the result. You know that I told you in the 
last lesson, that when dogs had been made to inhale either tannin 
or perchloride of iron, these substances had been seen to pass 
into the pulmonary parenchymas. Such animals have been at- 
tacked with bronchitis and with broncho-pneumonia, and have 
died from the effects. Under analogous conditions, Trousseau 
has seen an atomized application of tannin determine the most 
serious accidents, and a real broncho-pneumonia lay hold on the 
subject. 

What, then, is the process employed so as to avoid such acci- 



ATOMIZATION OF LIQUIDS. 

dents? In the first place, there is a natural and instructive pro- 
cess which may be mentioned. What I said to you a whi! 
of those sorts of spasms produced by mineral waters, of thai de- 
fence, so to say, which the respiratory organs offered, I mighl 
repeat with still more reason for solutions possessing an irritating 
chemical action. This defence reveals itself, then, by a real 
spasm; it is a way of preventing the liquid from penetrating 
into the depth of the respiratory organs. But, you will tell me, 
that this is a sorry process, unfavorable, in that the fluid has Qol 
even penetrated into the upper portions of the respiratory 
organs. 

The process for obtaining useful results without incon- 
veniences, is the following : when you recommend the atomizi 
a solution of tannin, or of nitrate of silver, in eases of chronic 
ulcerated laryngitis for the purpose of replacing the brush, the 
douche is to be taken in the ordinary way, but you must caution 
the patient not to breathe while the douche is in action, lie 
stops for a few moments, then applies the douche, so that the 
atomized water may enter into the most accessible and most ele- 
vated portions of the respiratory organs without permitting the 
dilatation of the thorax, to give it a chance to penetrate int.) 
their inner recesses. In other words, douches must be allowed 
to act by propulsion, and not by inspiration. 

It is not necessary to take all these precautions againsi the 
topical action of mineral waters, because, although they may 
present decided activities, those which we daily use have no con- 
siderable local effect. 

It would be absurd to say that mineral waters came 
medicaments, because they cannot be injurious, for there are 
waters that are so concentrated and of such intense activity, tint 
they constitute real poisons. I do not speak of the wat< 
Boucheterre, which contains as high as 20 grains of arseniate of 
soda in each litre, that is, more than tea times as much as those 
of la Bourboule ; but I have reference to a water which they 
call Riotinto, which contains sulphate oi alumina and peroxide 
of iron in such quantities that it may be -aid to be a natural 



124 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Vilate's solution. If you knew the effects produced by " liqueur 
de Vilate," you can form an idea of the power of this water. 

You must therefore remember that there might be disadvan- 
tages in certain cases in atomizing some mineral waters. Those 
that are generally employed have not this topical power. They 
are sulphur waters of all kinds, alkaline and saline waters, and 
mixed saline and arsenical waters. The sulphur waters are 
waters containing sulphide of calcium and sulphuretted hydro- 
gen, also mixed sulphides, like the EaUx Bonnes, which are 
intermediate between the sulphides of calcium and of sodium ; 
they are also waters containing sulphides of sodium, and cal- 
cium and alkaline at the same time. 

None of these are very powerful in their topical effects. Hence 
there is great utility, great profit, and almost no inconvenience 
where precautions are taken, in making use of them for inhala- 
tions. In a great number of establishments, only to mention 
those that are French, we see these inhalations of atomized 
waters long established and on a good footing. Among sulphur 
waters, properly so called, we have Pierrefonds, Enghien and 
Saint Honore ; in the Pyrenees, Eaux Bonnes, Luchon and 
Canterets ; Uriage, which is a saline and somewhat sulphurous 
water. Similar to it is that of Ussel, in the department of the 
Gard. 

We have in France a number of mineral waters which pos- 
sess a double mineralization ; they are both sulphurous and 
bituminous, that is, they contain a sort of fluid bitumen. These 
possess profitable application to a great number of affections, par- 
ticularly those of the skin. 

I will not say that they are very agreeable to take, but bath- 
ing in them produces excellent effects. They are also used in the 
atomized form, and they answer a double purpose — they pro- 
duce a useful astringent action and particular topical effects, due 
to the sulphurous principles which they contain. 

We also have alkaline waters in abundance : there is Vals 
with its forty odd springs, which offer a graduated scale in fixed 
principles from 50 grs. to 9 grs. in each litre. There is Vichy, 






• ATOMIZATION OF LIQUIDS. 125 

the queen of those waters. In these two great watering Btations 
they have established inhaling halls for atomized water, which 
render good service in affections of the throat, and especially in 
arthritic cases. You are aware that gout shows great variety in 
its effects. There are a certain number of affections due to this 
diathesis, which develop in the direction of the respiratory and 
digestive organs ; in these cases atomized alkaline mineral waters 
render real service. 

We also have a certain number of springs which I haved 
nated under the name of mineral nymphs, which produce all 
the salts that exist in the serum of the blood. Take water from 
Saint Nectaire and serum of blood, and you will find them t<> 
contain nearly corresponding quantities of salts. These wan 
which are no recent discovery, are pointed out to us by the m 
ancient tradition as serving to repair exhausted organisms and 
to improve persons afflicted with scrofula. They are also used 
in atomized form in affections incident to this prevalent dia- 
thesis. As similar in effects, I shall mention Royat and la Bour- 
boule. These are comparable to sea water. At ^rcachon, ;it 
Fecamp and at Trouville, we have atomizing and inhalations 
of salt water in a more or less nebulous condition. 

Let us sum up what we have just said with regard to the pre- 
cautions to be observed in atomizing mineral waters. 

The water must be at a mean temperature of from + 25 to 
+ 32°. It must be as finely atomized as possible, so that it maj 
in the highest degree penetrating. Furthermore, as theapparatus 
has not always the perfection you might desire, and as you 
must always suppose that you may meet with imperfect atomis- 
ing, the patient must be covered with a gown made 
impermeable material. Only under those conditions will 
secure the efficacy of the remedy without the possible liability 
of taking cold, to which persons were formerly 

I must now tell you of some of the applications of atom 
water, and of one in particular, quite recently introduced. I 
is the inhaling of a solution of sulphate of quinine by patients 
who could not take it by the stomach. 



126 PRINCIPLES AND METHODS OF THERAPEUTICS. 

It often happens that following a fever that has required 
large quantities of sulphate of quinine, there is developed such 
an intolerance of the stomach, that it becomes unable to retain 
the drug which, however, may be necessary for the cure of the 
patient. Prior to our having bromo-hydrate of quinine, which 
is an inoffensive form of quinine for introducing into the sub- 
cutaneous cellular tissue, efforts were made to devise a plan for 
the introduction of the sulphate otherwise than by way of the 
stomach ; among others, inhalation of quinine was suggested. 
Mr. Ancelon caused a solution of 500 grains of water con- 
taining 1 grain of sulphate of quinine to be atomized at the 
home of a patient in two sittings during the day, and he had the 
satisfaction of not seeing any return of the fever, which yielded 
as it would have done to doses taken into the stomach. This 
example has been imitated by Mr. Bujon, who has used the same 
process and obtained a sudden cessation of the fever. These facts 
are at present less interesting, because we have the hydro-bromate 
of quinine, but, nevertheless, they still retain a real physiological 
interest. 

Atomization of artificial solutions or of mineral waters, has 
been employed for other purposes than inhalations, as in ocular 
affections of old standing, which have resisted other means. 
These douches upon the opened eye-lids have given good results. 
Mr. Pigeaux has attempted treating cases of endometritis 
by atomized solutions of nitrate of silver. He has met with 
comparative success. The plan has some advantages : in the 
first place, an atomized douche has not the force of an injection, 
properly so called ; it does not give rise to accidents from fluids 
entering the interior of the cavity of the tubes, and in conse- 
quence it does not produce those more or less serious and at times 
fatal accidents induced by active substances ; besides, by the very 
fact of this atomizing process, the whole surface of the uterine 
cavity is acted upon by the medicament. 

If a moderately concentrated solution is used, an atomization 
is obtained which is beneficial in those cases in which the mucous 
membrane presents a resemblance to velvet, and is highly vascu- 



ATOMIZATION OP LTQCIDS. ] -j 7 

larized and bleeding. When there are fungosities, it ue 
dently better to follow Mr. Richet's process, which is no other 
than that of Lallemand, of Montpellier, and which consists in the 
introduction of a caustic holder, so shaped that the whole sur- 
face is cauterized. 

I add but one word more, in relation to what has been called 
" aquapuncture." The idea was conceived of using a verv fine 
water jet obtained by the aid of pressure of not less than lour or 
five atmospheres, for the purpose of percussing the surface of 
the skin, and obtaining not merely a pricking sensation, not only 
a bright redness on the spot which was the seat of percussion, 
but also for actually perforating the skin. 

Some years ago I gave my audience an opportunity of wit- 
nessing these effects, by piercing in their presence leather of con- 
siderable thickness. Hence, as you see, this is rather a violent 
process, and one whose action is difficult to measure. And to 
obtain what? About the same effects as by the aid of the most 
easily handled topical irritants, like puncturing with needles — 
and, moreover, often without any therapeutic results. It was 
my duty to mention this absolutely useless process, which any- 
how, we may say, is forgotten by the majority of the public 



128 PRINCIPLES AND METHODS OF THERAPEUTICS 



CHAPTER XL 
Open Wounds — Cutaneous Methods. 

Absorption through Wounds ; Absorption by the Serous Cavities. 
Cutaneous Absorption — Fallacy of the arguments advanced in favor of absorp- 
tion through the unimpaired skin ; refutation of those arguments. 



Gentlemen : 

We have concluded tne study of the mucous tracts, as avenues 
for the introduction of medicines. I have now a word to say 
on the pseudo-mucous membranes, which are those found in 
mucous tubercles, in burrowing wounds and in fistulas. 

It may be said that these are, from a functional point of view, 
true mucous membranes, which may become surfaces for absorp- 
tion. At times, this is very obvious. When, for example, sur- 
faces covered by mucous abrasions of syphilitic origin have been 
cauterized, these surfaces being of great extent, it has happened 
that acute hydrargyrism of the most intense kind has been ex- 
cited, together with painful and foetid stomatitis, followed by un- 
pleasant sequelae. This absorption, however, becomes a favorable 
circumstance in effecting a thermal cure. It has been observed 
that in these thermal cures, which are effected with saline waters 
holding iodides and bromides in solution, the patients who de- 
rive the greatest benefit are precisely those who were most 
seriously affected. Thus, you send scrofulous patients to seek a 
cure either at Kreuznach, or at Salins, or at Sal is de Beam, and 
you observe that those patients are the most relieved who pre- 
sented in appearance the most serious accidents. If they only 
have, as yet, ganglionic enlargements, they will no doubt derive 
benefit from tonic mineral waters; but if they have fistulous 



OPEN WOUNDS. CUTANEOUS METHODS. 129 

courses, ulcerations on the lower limbs and on the neck, by 
having them plunged into these stimulating waters (to which are 
added what are called the mother liquors, which are more highly 
iodo-bromized than the water itself,) these patients will derive 
really wonderful benefits. The ulcerated surfaces are soon modi- 
fied ; they regain their color ; the tissues become healthier, while, 
at the same time, the secretions become more regular and assume 
a more satisfactory character. The patients owe these improve- 
ments in their conditions to the presence, on the periphery of 
their bodies, of surfaces as capable of absorbing as are the 
mucous membranes themselves. 

There are also circumstances in which the serous cavities be- 
come a seat for the absorption of medicaments. For example: 
it not rarely happens that when an injection is thrown into the 
vaginal tunic, of a mixture of water and tincture of iodine, such 
rapidity of absorption is sometimes developed by the serous mem- 
brane which has been touched by the injection, that the patients 
are taken with real, genuine, acute iodism — watering of the eyes, 
intense coryza, and such an obstruction of the nose that they are 
hardly able to breathe. 

I shall now speak of medicamental introduction by the cuta- 
neous periphery. There are distinctions here to be made. At 
times, the skin is unimpaired ; again, it is deprived of its epithe- 
lium ; at other times, the introduction is made within the thick- 
ness of the dermis; or, finally, by the subcutaneous cellular 
tissue. 

Let us first speak of the introduction of medicaments through 
the unbroken skin. A debated question here arises. Is the 
unimpaired skin an avenue of absorption for medicaments; and 
if it is one, for what substances, and in what quantities? This 
question has been solved in very different ways. There are cir- 
cumstances which prove that absorption takes place through the 
unimpaired skin, and there are others which demonstrate the 
contrary. We must distinguish the chaff from the good grain. 
We must always, to some extent, refer ourselves to physiology, 
and you know it is generally in that way that I commence the 

I 



130 PRINCIPLES AND METHODS OF THERAPEUTICS. 

study of medicaments. What does physiology teach us as to the 
possibility or impossibility of absorption through the skin? It 
teaches us that the skin is provided with a very delicate apparatus, 
and is a vigilant sentinel, which not only warns us against what 
may harm us, but also that it is a medium by the aid of which 
we have the sentiment of self so strongly developed that when- 
ever its sensation is abolished, we lose this sentiment. It is 
under these conditions that Saint Theresa and other persons 
have believed that they no longer had a body distinct from that 
of the universe, but that they had united themselves with the 
divinity. The skin is intended to protect the rest of the body, 
and you know how great is its protecting power, since when an 
injury has produced considerable lesions beneath it, it may remain 
intact, or at least present much smaller lesions. The skin is at 
the same time an organ for secretion, but it is an organ for ex- 
crementitious secretion ; what it ejects is not destined to re-enter 
into the organism. It is an annex to the respiratory apparatus, 
not that the phenomena which take place upon the surface of the 
skin can be compared to those of cutaneous respiration among 
batrachians — no; but the skin is nevertheless an organ through 
which interchanges are made. For this reason it is necessary to 
recommend cleanliness, baths, frictions. Keeping up the cuta- 
neous function is doing an important service with regard to 
hsematosis itself. From what we have just said of the physiology 
of the skin, can it be supposed that it is a very energetic organ 
for absorption ? No ; and even it may be said, a priori, that it 
can only be a surface of absorption for substances analogous to 
those that are exchanged, in a normal way, through its pores. 

You will see that what physiology indicates as probable is 
demonstrated by the observation of facts, and consequently you 
see how useful it is always to take it as our guide and our beacon 
in all pathological and therapeutic questions. 

I was saying that we could only look for the absorption of 
volatile or gaseous substances. And yet, from all time, it has 
been the custom to apply upon the skin all the substances which 
the stomach refused to accept, and experiments show that a cer- 



OPEN WOUNDS. CUTANEOUS METHODS. 



131 



tain number of successes obtained led easily to entertaining illu- 
sions upon its absorbent powers. 

Four lines of argument have been advanced in support of the 
reality of this absorption. It was said that upon the applica- 
tion of medicaments to the cutaneous periphery, it has been 
noticed that similar physiological and therapeutic effects were 
produced, as would have been the result had the introduction of 
these same medicaments taken place through the stomach. Again 
it was said, that there was a certain proportion of the substances 
applied upon the skin which had disappeared, as though absorbed 
by it. It was added that when substances with which bodies 
were in contact, were in sufficiently considerable masses, they 
could be absorbed in such proportions that there would result an 
increase in the weight of the body. Finally it was stated that 
in a certain number of cases substances applied to the cutaneous 
periphery had been detected either in the blood or in the urine. 

These are the four lines of argument invoked in support of 
cutaneous absorption. We shall take them up singly, to ascer- 
tain their value. Let us speak of effects said to have been ob- 
tained by the aid of medicaments applied to the periphery. There 
are here certain facts which must be reviewed. 

At a remote period it was observed that baths or poultices 
laden with emollient or narcotic principles, and that topical 
applications, consisting either of cold or of astringent substances, 
produce positive effects. And it was said that if those substances 
applied upon the abdomen or on the periphery of the body had 
determined, some soothing and sedative phenomena, others stimu- 
lating and resolvent phenomena, it was probably because these 
substances had penetrated the system, there to produce the effects 
of which they were capable. 

Th°v forgot but one thing — that there is a sympathy of con- 
tinuity and contiguity, as John Hunter called it; that there are 
incessant exchanges of stimulation and of sedation between the 
tissues of two neighboring regions, by virtue of what I have 
designated by the name of polarization. And that, I repeat, ex- 
plains in great measure the calming or tonic phenomena pro- 



132 • PRINCIPLES AND METHODS OF THERAPEUTICS. 

duced by the application of certain#substances on the surface of 
the body. 

For example, if it is desired to allay a colic, a warm poultice 
is applied, and it is by some believed that the poultice is capable 
of producing a deep sedative effect, by the penetration of its con- 
stituents. No; it has been obtained by the process I have just 
indicated, and by reflex action, for which, however, too much im- 
portance has been claimed. You may read SchifTs experiments, 
read Vulpian's work, and you will see how evident is the exist- 
ence of reflex phenomena between the different peripheric and 
the deep-seated regions, and how one side of the body is in sym- 
pathy with the other side. Already Brown -Sequard had 
pointed out that when one hand is cooled the other is cooled also. 
But here a distinction is to be made : When the excitations are 
of very great violence, contrary phenomena are shown on the 
part of the deep-seated organs. If an intense cold is applied, 
there is produced a real paralysis of the deep-seated vessels in 
the parenchyma of the internal organs. 

This explains those a repercussions " which are produced when 
intense cold has been applied to the periphery. On the contrary, 
when there is a moderate peripheric impression, whether its nature 
be to produce a relaxation of the vessels or a vascular contraction 
is of but little moment ; it is an analogous phenomenon which 
produces itself within the organs. If, for example, you apply 
upon the abdomen a moderately cold body, you will contract the 
vessels in the deep-seated parts. If you apply upon it something 
warm, which gives rise to greater capillary vascularity, an analo- 
gous phenomenon will be produced in the deep parts. You then 
understand how it is that by the agency of these reflex actions, 
substances which exercise no actions but through their physical 
qualities, may determine sedative phenomena within the depths 
of a region upon which they are applied. Purgative effects have 
been spoken of as produced by the external application of certain 
substances, and some of the most illustrious names are quoted in 
support of facts of this kind, as those of Haller and Soemmer- 
ing, and also of Seguin, whose name is more modest. It has 



OPEN WOUNDS. CUTANEOUS METHODS. 133 

been said that by the aid of drastic substances, such as calomel, 
castor oil or croton oil, applied on the cutaneous periphery, ener- 
getic purgative phenomena are produced ; that other substances 
applied upon the skin have induced the expulsion of helminths. 
Even neutral salts have been supposed capable of acting by way 
of the cutaneous periphery. 

These are statements, of which two categories may be made — 
those which are altogether impossible, and the others which, 
without being impossible, are altogether improbable. I apply 
this to the story of the neutral salts. Supposing that these salts 
when deposited on the surface of the skin, had the power of pro- 
ducing effects through it, let us see if, when absorbed, they could 
determine the purgative effects attributed to them. No. We 
know ever since the experiments made by Moreau and repeated 
by Eabuteau, and we have also learned by clinics, that when 
neutral salts are introduced in the blood, and go to increase the 
proportion of those which are already there, not only they do 
not determine purgation, but they produce constipation. I say 
that we have known this for a long time, and all physicians who 
practice in the neighborhood of mineral waters know that when 
waters highly charged with salts and capable of purging, are 
taken in such proportions that purgation does not immediately 
follow, whenever, in a word, the subject resists their effects, not 
only the subject is not purged, but he is constipated. That is 
what happens at Carlsbad, at Hamburg and at Kissingen, when 
those waters are taken by half glassfuls, and they do not purge. 
Persons who had a stool once a day no longer have any. These 
waters are both purgative and constipating, according to the fol- 
lowing process : 

The salts not being eliminated are absorbed j they go to 
swell the proportion of salts in the blood, and thereby oppose 
themselves to increased serous secretions. 

This is what we likewise observe at the French thermal stations, 
which, in lesser numbers, are gifted with purgative properties. 
We also know that the different waters used as purgatives, such 
as Pullna and Siedlitz, and which are in abundance at the present 



134 PRINCIPLES AND METHODS OF THERAPEUTICS. 

day, are constipating, when given in insufficient doses to produce 
purgative effects. Freiderichshall water is even given as a re- 
storative, as a means of increasing the proportions of salts in the 
serum, in cases of albuminuria. Here are cases, therefore, in 
which the phenomena that have been attributed to cutaneous 
absorption could not have taken place. 

There are others whose occurrence is improbable. Here is 
rhubarb, a drastic root, of which a large quantity is required in 
order to purge. How can we admit that applied upon the skin, 
it could have produced physiological effects ? The case is not 
altogether the same with calomel and croton oil. Calomel is a 
mild sublimate. It is, therefore, a volatile substance, and if it 
is a volatile substance at -|- 37.5°, it can be sufficiently volatil- 
ized so as to be absorbed by the respiratory organs. But sup- 
posing that calomel could have been absorbed in small quantities ? 
It would have, at most, produced alterative effects. There is, 
besides, a coincidence, against which we should be on our guard, 
to wit, that of a natural clearance, but which is credited . to the 
substance employed. Great stress has been laid upon the effects 
of croton tiglium applied on the skin. It is a complex substance, 
which contains both a fixed oil and an essence. It is therefore 
evident that if an extensive friction has been made and if the 
patient remains covered up in bed, this may determine phenomena 
of irritation in the tract of the digestive duct. But here, I 
think, fallacious coincidences have been met with. 

Other medicaments have been spoken of as capable of being 
absorbed by the skin, among them mercury. Yes, the mercury 
which exists in mercurial ointments is absorbed, and we shall see 
further on in what way. Although mercury is not very volatile, 
it emits vapors at 15° below 0, hence, still more so at 37°. 

Consequently it is readily understood that when an extensive 
friction is made, as in peritonitis, or in the case of syphilitic 
patients, in both arm-pits, the patient may absorb sufficient vapor 
to exhibit the diffused effects due to mercury. But we shall 
presently see that it is also absorbed by the skin. 

Great stress has been laid upon certain cases of poisoning said 



OPEN WOUNDS. CUTANEOUS METH DS. 135 

to have been produced either by extract of belladonna, or by 
poultices of tobacco leaves, applied upon the abdomen. There 
are here two causes of error. You cannot prevent persons upon 
whose abdomens extract of belladonna has been applied, from 
putting their hands there, and then carrying them to their eyes. 
This would account for the pupillary dilatation. I add, that the 
alkaloids from belladonna and from tobacco are volatile sub- 
stances. Therefore, I think no importance should be given to facts 
of this kind, for the purpose of showing cutaneous absorption. 

Iodide of potassium is also a substance which has given rise 
to modifications in the urine, indicative of its passage. We shall 
see how this phenomenon is produced. But at all events it is not 
iodide of potassium in solution that can be absorbed. Arsenic, 
cantharides, tartar emetic — these are all substances said to have 
been absorbed. But I would have you remark that all those 
substances are only absorbed after friction. 

With regard to cantharides, there is, in the first place, a more 
or less intense inflammatory irritation, a secreted serosity which 
takes up the cantharides, after which the dermis absorbs the 
serosity. Here absorption takes place of a serosity laden with 
cantharidine, and, besides, the skin is no longer unimpaired. 

The same is true of arsenic, which produces inflammations and 
eschars. It leads to mortification, but not to the chemical trans- 
formation of the tissues, which are still recognizable, after having 
been killed by arsenic. But, anyhow, it forms eschars, and when 
once it has thus penetrated it can be absorbed by the vessels in 
connection with the eschar. I shall say as much for tartar 
emetic, which gives rise to those pustules which you all know, 
and which is likewise only absorbed by means of frictions. Con- 
sequently, all this does not apply to the unimpaired skin, and 
hence is of no applicability to the question now occupying us. 

I come to the argument concerning the disappearance of a cer- 
tain quantity of the substance placed on the surface of the skin. 
It is Seguin, especially, who has introduced this new notion. I 
do not think that he has rendered thereby any great service to 
science, or adduced any positive facts to support it. He ini- 



136 PEINCIPLES AND METHODS OF THEEAPEUTICS. 

merses his arm in a local bath, and he observes that when the 
bath has been sufficiently prolonged, the weight of its water 
having first been ascertained, there is a loss in that weight. Cer- 
tainly, there must be a loss. There you have an arm at a tem- 
perature of 36°; you immerse it in a local bath; of course, a 
certain proportion of the water must be volatilized. This ex- 
periment is absolutely worthless. 

He also made others, which consisted in placing on the skin, 
under watch crystals, so as to maintain them in close con! act with 
it, scammony resin, calomel and tartar emetic. After the con- 
tiguity had lasted ten hours, he found the scammony had lost 
one-fourth of a grain, the calomel two-thirds, and the tartar 
emetic 5 grains of a total of 72 grains. Do you believe, gentle- 
men, that the disappearance of gr. .J of scammony proves any- 
thing? It is only necessary that the spot should have been 
carelessly wiped off; gr. .\ is something so very small. 

In the other case, I cannot admit that 5 grains of tartar emetic 
could disappear without considerable phenomena having re- 
sulted therefrom, such as pustules with central eschars. All 
these effects should have been produced if the action upon the 
skin had been really energetic, and sufficient to explain the dis- 
appearance of gr. 5 of tartar emetic. 

I believe that there were errors in the weighings. There may 
have been imbibition by the epithelium of the solution, and an 
impossibility of removing the substance — owing to adhesion 
to the epidermic coating; perhaps, even destruction of the 
salts, but assuredly there was no absorption. All the experi- 
ments which we make at the present day demonstrate in a 
peremptory way, that absorption, under those conditions, would 
have been impossible. 

But there is another grand argument, the main dependence of 
those who admit cutaneous absorption. In a bath the body in- 
creases in weight. This increase is not enormous; it is from 40 
to 50 grammes. You will tell me that this is a good deal ; but 
I maintain that it is little, if you reflect upon the surroundings, 



OPEN WOUNDS. CUTANEOUS METHODS. 137 

which cannot fail to remove from the bath a certain proportion 
of the water it contains. 

You know that after a bath that has lasted an hour, and even 
less, your skin is all wrinkled, because the epithelium is tumefied ; 
you have only to look at your fingers ; the epithelium has become 
white, opaque, swollen. The result is a corrugation comparable 
to the cerebral convolutions, proportioned to the degree of imbi- 
bition of the epithelium. Therefore, the epithelium of the palm 
of the hands and the soles of the feet imbibes, and you can form 
no idea how much water this imbibition represents. When you 
will happen to have under your care patients suffering from in- 
tense scarlatina, from whom you can remove a gauntlet formed 
out of the epithelium, remove it, and after having dried and 
weighed it, wet it and weigh it a-fresh. You will then see, if 
you multiply the result by the surface of the feet and hands, that 
the amount obtained is almost sufficient to account for the quan- 
tity of water that has been absorbed in a protracted bath. 

I have made this experiment, and have ascertained that the 
amount is considerable. Messrs. Delore and Hebert repeated 
the experiment, and came to the same conclusions ; that is, that 
according to all experience, the water which impregnates the epi- 
dermic coatings of the hands and feet, together with that which 
remains on the surface of the body, is sufficient to account for the 
increase in the weight of the body. Besides, when you come out 
of a bath, believing yourself immaculate, if a shampooer takes 
charge of your person, he will prove to you that you still have 
grammes of epidermic matter on the body. This matter is no 
longer alive, but as it adheres on the surface of the skin, it is still 
capable of absorbing a considerable quantity of water. That is, 
therefore, another argument which we are obliged to lay on the 
table. But there is the scientific argument. This is, as I told 
you, the presence in the blood, or io the secretions, of substances 
deposited on the surface of the skin. There have been a gn at 
many experiments made, and with different substances, to prove 
this passage into the blood. Ferro-cyanide of potassium, which 
is often used because of its reactions, has been employed, and it 



138 PRINCIPLES AND METHODS OP THERAPEUTICS. 

is said to have been detected in the blood and in the secretions. 
I rest satisfied here, with the expression of a doubt. I believe 
in the possibility of absorption in certain cases, but to establish 
in a rigorous manner that it had been absorbed, it is not suf- 
ficient that the thing is possible, especially as it has been proven, 
that there is in the economy a substance more or less analogous 
to cyanide of potassium. Remember that there are sulpho- 
cyanides in the saliva, and that Prussian blue may be formed at 
the expense of the blood. 

You see that those investigations, based upon minute quan- 
tities of substance, are surrounded with uncertainties. On this 
score, I reserve my doubts. 

It is said that the coloring matters of madder and of rhubarb 
have also been detected. For us who know how numerous are 
the coloring matters in urine, who know that there is a urinary 
indigo, and substances analogous to those that are derived from 
aniline, we cannot attach importance to reactions that are at least 
doubtful and made under such conditions. 

It has been said that water penetrates not only because we find 
that the body augments in weight, but because we observe an 
increase in the urinary discharge. Nothing of the kind takes 
place. The urinary discharge is increased, not because a greater 
quantity of water has penetrated, but by virtue of reflex actions 
which bear upon the sensibility, and on the renal vessels, and 
vascular tension. This is so true that at the same time that pro- 
tracted baths are regarded as giving rise to more urine, they give 
rise to alkaline urines. Odd, indeed, if those alkaline urines 
had shown themselves following Vichy water baths. What a fine 
argument ! It had then been evident that not only water was 
absorbed, but it also carried along its salts ! There is but one 
misfortune; it is, that with alkaline baths no alkaline urines are 
given, but they appear after baths containing nitric acid. There- 
fore, it is not the absorbed alkali which has given the reaction to 
the urine. I merely add that the occurrence is still of difficult 
interpretation. The fact is true; it cannot be denied; it has 
been witnessed by several distinguished observers. All those 



OPEN WOUNDS. CUTANEOUS METHODS. 139 

who have submitted themselves to protracted baths of this kind 
have obseived it. 

It is probable that under those conditions a phenomenon takes 
place comparable to that which exists in convalescence. In this 
state, there is a period during which the urines are always alka- 
line, so much so that when you find a patient in full convalescence, 
with reduction of temperature, and you ask for the urine, it is 
uniformally alkaline. 

It seems to me that protracted baths produce upon healthy 
subjects conditions somewhat, or perhaps altogether, analogous to 
those exhibited by convalescents, in whom there is a profound 
sedation of all organic acts. 

But there are other facts which have had greater notoriety, 
and which appear more precise and more scientific. They are 
those observed by Mr. Willemin, and by the regretted Hirtz, of 
Strasbourg. These two talented and conscientious men applied 
themselves to examining what took place when a subject was im- 
mersed in a bath containing sublimate, or iodide of potassium, 
and they came to the conclusion that the skin absorbed, con- 
trary to all adverse testimony. They examine the urines of per- 
sons who have remained in a sublimate bath, and find nothing 
in them. They make their observations upon baths containing 
100, 200, 300 grammes of iodide of potassium, and often note 
negative results and sometimes positive results. You, no doubt, 
suppose that after this they should have said to themselves the 
skin is not an available absorbent. Not at all ; they adhere to 
positive facts, lay the others aside, and conclude that the skin is 
a comparatively fair absorbent, and that baths can introduce into 
the economy more or less considerable quantities of the principles 
with which the water is laden. 

I shall discuss this conclusion in the next lesson, and show 
you how faulty it is. 



140 PKINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XII. 
Cutaneous Method.— Baths. 

Cutaneous Absorption [continued]. — Explanation of contradictory facts 
and opinions. 

The skin absorbs under certain conditions. — Action of fatty bodies. — Vola- 
tile substances. — Action of the law of gaseous diffusion. 

Processes adapted to favoring absorntion through the skin. — Special activity 
of certain regions. 

Medicinal baths : their value. 



Gentlemen : 

Mr. Koussin 1 has demonstrated that by placing yourself under 
favorable conditions, the iodide of potassium contained in a bath 
is never absorbed through the skin. That is to say, if your skin 
is perfectly unimpaired, if you wipe yourself thoroughly, and 
especially if you take an ordinary bath after the iodized bath, 
there will be no iodine in the urine. On the contrary, he has 
demonstrated that when you make use of a solution of iodide 
of potassium in the proportion of a tenth, and apply it upon 
certain regions of the body, allowing it to dry upon you, or else, 
if you pulverize iodide of potassium and dust it on your under- 
shirt, under those conditions iodine is always observed in the 
urine. 

How, then, explain such contradictory facts? To my mind, 
the explanation is a simple one ; here is what takes place : after 
you have, so to say, daubed over the surface of the body, the 
axillary regions, for example, with a concentrated solution of 

koussin. Double Poisoning by Schweinfurth Green. New Experiments 
Relative to Cutaneous Absorption. (Ann. d'Hyg., 1867, 2d Serie, tome 
XXVIII., p. 179.) 



CUTANEOUS METHOD. BATHS. 141 

iodide of potassium, or when you have applied to the periphery 
powdered iodide of potassium, at the end of a certain time you 
can no longer find it. Do you know what color is assumed by 
ointment made out of fresh lard and iodide of potassium ? This 
ointment, which at first is white, gradually becomes yellow, then 
changes to a more or less reddish -brown. What is it that takes 
place in the case of this ointment, which finally becomes brown 
and of a disagreeable odor? This is what has taken place: 
however fresh was the lard, it has finally grown rancid, and the 
fatty acids have gradually liberated the iodine previously com- 
bined with the potassium. It is iodine that is liberated, and it 
denotes its presence by its coloring and its smell. When you 
apply iodide of potassium on the surface of the skin, the same 
phenomenon is produced and in the same way. Remember that 
perspiration is an acid liquid containing volatile fatty acids of 
sufficient energy to act upon litmus paper. When iodide of 
potassium is in contact with the skin, it is decomposed and iodine 
is liberated. But it is a volatile substance, consequently we can 
apply to it the remarks we made at the opening of the preced- 
ing lesson, when, in considering other substances of a similar 
kind, we supposed it was possible for them to be absorbed by 
the respiratory organs. 

We therefore say that it is possible that the iodine set free 
under the influence of the acids from perspiration, should be 
absorbed by the respiratory organs, and not by the skin. 

This leads me to tell you that iodine in the metalloid state can 
really be absorbed by the skin. 

Thus far I have only shown you negative results, and given 
you to understand that all anterior conclusions were hasty and 
faulty. I shall now demonstrate to you that there are sub- 
stances which are absorbed through the skin. 

For this purpose iodine supplies us with the most perfect 
means of demonstration. When iodized cotton is applied, and 
the region it covers is enveloped in an impervious dressing made 
of adhesive plaster or thin layers of gutta percha, and finally 
bound over with a bandage of flannel, so as to maintain the 



142 PRINCIPLES AND METHODS OF THERAPEUTICS. 

whole and exclude the air, we find that iodine is absorbed, and 
it shows itself in the urine after a lapse of time. 

I must confess that when I made these first experiments, 
originally with tincture of iodine, I was especially impressed 
with its penetration into the economy and its diffusion, when the 
epithelium covering the region appeared to me to have suffered 
deep alteration. But I have since made other experiments, from 
which there results the possibility of two cases presenting them- 
selves, the one to which I had at first attached importance, 
and another, which is the following : you may make the appli- 
cation around the hand, surround it with an impervious muff, 
and absorption will take place although nothing on the dorsal 
surface of the hand, hence much less so on the palm, will the next 
day reveal the existence of any lesion of the epithelium; and 
the proof is, that there is no desquamation even with the most 
concentrated tincture of iodine. There are, therefore, cases in 
which the absorption of iodine takes place, although the epithe- 
lium is unimpaired. 

It is very easy to prove the existence of iodine, or, at least, a 
combination of iodine, in urine. This very simple process con- 
sists in pouring commercial nitric acid, little by little into the 
glass containing the urine to be tested, and then dipping to 
the bottom of the glass a piece of paper. Provided that this 
paper be of finely divided cellulose (it is not even necessary 
it should be starched,) it will, under the influence of the acid, lib- 
erate the iodine held in combination as an iodide, and that will 
then impart a blue color to the paper. It is therefore very easy 
at present to demonstrate that iodine has been absorbed through 
the skin, even without any alteration of the epithelium. What 
takes place with iodine may occur alike with all similar vola- 
tile substances, and this confirms the opinion derived from 
physiological considerations, which I spoke of at the opening 
of the last lesson. 

I told you the skin was a vicarious agent of the respiratory 
organs — it absorbs gases and volatile substances alike. Of this 
we have an almost rigorous demonstration in the mercurials. 



CUTANEOUS METHOD. BATHS. 143 

As you know, I have sometimes caused mercurial frictions to he 
made in the palms of the hands, care being taken to envelop 
these in an impervious dressing, and I have thus obtained 
absorption and positive therapeutic results. A greater number of 
experiments are desirable, but there are few syphilitic patients 
ready to lend themselves to this treatment. However, I repeat, 
that at present it is fully demonstrated, rigorously in some 
cases, in others with a near approach to scientific rigor, that vola- 
tile substances can be absorbed by the skin. Thus formic and 
valerianic acids, ammonia, and such volatile substances as musk, 
camphor, castoreum, and others containing these principles, may 
be absorbed by the sudoriparous glands. Likewise all volatile 
organic alkaloids, as those from the hemlock, and generally all 
those from the poisonous umbelliferse, cicutine, coniine and 
conicin. The same is true of nicotine, atropine and duboisine, a 
new alkaloid obtained by Gerhart, in England, and in France 
by M. Petit. 

The question is, how does this absorption take place ? I gave 
its theory long since. It has been lately renewed in Germany, 
I was about saying, taken from me, but I prefer believing that 
it has been re-discovered. As early as 1869, I published an 
article on this subject, showing we could here apply the law of 
gaseous diffusion, which says : when a gas penetrates into a con- 
fined space, it diffuses itself in equal proportions throughout the 
whole atmosphere of that space. This explains how gases 
coming from the blood are diffused in the atmosphere, while 
those from the atmosphere, diffusing themselves in the sudori- 
parous ducts, may be absorbed by the glands. It is, therefore, 
the theory of diffusion which I have applied to particular g 
Newman, in 1871, expressed the same thought, and explained, 
by this diffusion, the action of gases. This proves the correct- 
ness of my opinion. 

Are only volatile substances absorbed through the skin ? The 
skin is capable of absorption when active substances are in solu- 
tion, or in an intimate mixture equivalent to solution. Thus 
camphor is not soluble in water, yet we have camphor water, 



144 PRINCIPLES AND METHODS OF THERAPEUTICS. 

that is, camphor vapor in a molecule of protoxide of hydrogen. 
There are substances also, which, although insoluble in fatty 
bodies, yet enter into such intimate mixture with them that they 
are carried wherever these bodies go. This is the case with 
many liniments. Active substances when in solution in fatty 
bodies, may penetrate through the epidermis in contact with the 
superficial vascular elements of the dermis, and be more or less 
absorbed. 

The more clearly to understand these interesting phenomena, 
you have only to remember what happens with a filter which 
has first been saturated with oil. When you throw upon it a 
mixture of a fatty body in an aqueous solution, the aqueous solu- 
tion remains and the fatty body filters through. The same hap- 
pens when a mixture consisting of an aqueous matter and a fatty 
substance holding in solution active principles, is brought in con- 
tact with the epidermis more or less impregnated with fatty 
matters, the fatty matter passes through this filter, but the sub- 
stance in the aqueous solution is not admitted. That is the first 
case. Another is, when this epidermic barrier is either made 
thinner or modified in its chemical composition so as to become 
permeable. It may be made thinner by frictions; hence these 
have often been recommended for the purpose of favoring 
the absorption of substances incorporated with fatty matters; 
such frictions, when by a vigorous hand, sometimes result in an 
abrasion of the epithelium. Absorption then takes place through 
the superficial coating of the dermis. 

But there are other methods by which the thickness of the 
obstacle may be reduced. For example, the epidermis is not 
entirely composed of living layers ; there are on its surface old 
layers, either dead or in process of separation. Alkalies are an 
excellent agent for the removal of this layer which forms an 
emulsion with the fatty matters of tallow ? hence it is advisable 
to wash with soap the place through which absorption is desired. 
The epidermis may also be made more permeable by the action 
of acetic acid on the surface of the body, this acid, as you 
know, possessing the faculty, if not of dissolving at least of 



CUTANEOUS METHOD. BATHS. 145 

softening, and hence of greatly reducing the state of impervious- 
ness of the epithelial cells. So energetic is this action that there 
are popular remedies for the removal of callosities, corns 
and bunions, which consist mainly of acetic acid. 

There are also other methods, such as rubefacients, which are 
often recommended for the purpose of favoring cutaneous absorp- 
tion. By their use the skin first reddens, and the small vessels 
are dilated, but this is not the important feature. Following 
this artificial inflammation there is a considerable desquamation 
of the epithelium, which at times falls off in large shreds, and 
there remains a reddish surface covered over with a thin 
epithelium, which absorbs rapidly. Such are the ways of reduc- 
ing epidermic resistance. The epidermic coating may also be 
made permeable by freeing it from the substances that cover it. 
For this purpose ether, chloroform, sulphide of carbon, in fact 
all substances acting as solvents of fatty bodies may be used. 
Protracted maceration in water, as in the case of baths lasting 
two hours, gives opacity to the epidermis, which becomes more 
permeable, and may thus give passage to a small proportion of 
the substances held in aqueous solution. This would justify 
those who believe in the penetrability of active substances dis- 
solved in water. It is of no practical benefit, however, because 
the quantities of active substances introduced are infinitesimal, 
and no reliance can be placed on their effects. 

The whole discussion may be thus summed up : gaseous, or 
volatile substances are highly absorbable by the skin, and they 
are still more so when more decidedly gaseous or under the form 
of volatilized substances. On the contrary, substances simply 
soluble in certain vehicles pass through the skin with comparative 
difficulty. When soluble in fatty bodies, they may penetrate to 
the superficial net- work and be absorbed. When dissolved in 
water, absorption is almost impossible, or takes place very slowly. 
Here, however, a distinction comes in, which I have already 
made. 

There are regions in which the epidermis does not present so 
serious an obstacle to the absorption of substances ; these are the 

K 



146 PRINCIPLES AND METHODS OF THERAPEUTICS. 

hands and the soles of the feet. Here there are no sebaceous 
glands, no fatty coating, hence favorable conditions for gaseous 
and aqueous absorption exist, more so for the former than the 

latter. 

I may say as much of other regions, like the groin and the 
arm-pit, both often selected by partisans of the cutaneous method. 
Those regions are not under the same conditions as others, as in 
place of sebaceous glands there are bunches of glands, well de- 
scribed by Ch. Eobin, 1 secreting a product which is not sebum. 
Consequently, these glands do not lubricate the epidermis, as is 
the case in other regions, and the absorption of substances dis- 
solved in water is therefore much more active. 

The practical indications for grading the different substances 
which may be placed in contact with the cutaneous periphery, 
are as follows : Aqueous solutions of active principles, taken 
from the mineral or organic kingdom, should not be entrusted to 
cutaneous absorption, unless they contain very active substances 
like acetic or hydrochloric acids, but as these are highly active, 
from a chemical point of view, patients are not usually subjected 
to them. 

Volatile substances may be absorbed through the skin. A 
solution of morphine, or of nicotine, may be applied to the 
periphery of the body and absorption be possible, since the or- 
ganic substance is volatilized ; whether it passes through the 
respiratory organs or through the sudoriparous glands, it can 
enter into the economy. 

Nothing should be expected from that long list of methods for 
which good results are claimed, such as poultices containing 
narcotic substances, lotions, fomentations and local baths. All 
those give nearly negative results. Almost as much may be 
said of general baths, and this is important, because you daily 
prescribe baths with arseniate, or carbonate of soda, or of natural 
mineral waters, always under the belief that a more or less 
active absorption will take place, producing effects similar to 

1 Robin. Medical Dictionary, (14th ed.) Paris, 1878, p. 679. Article, 
"Glands." 



CUTANEOUS METHODS. BATHS. 147 

those which would have followed the introduction of those active 
principles through the digestive organs. 

The experiments made at Strasbourg and elsewhere only tend 
to continue this general error. I cannot uphold that view, and 
in this I am in accord with numerous authorities, particularly 
with almost the whole Medico-hydrological Society, in which a 
commission was appointed, which has reached conclusions similar 
to those I now announce ; that is, that there is no absorption 
from baths, and it is needless to exp3ct any. Therefore, I unite 
with Scoutetten in saying that arsenical baths should not be pre- 
scribed, with the belief of obtaining general results, and I add, 
except it be in the case of women, or of subjects affected with 
more or less intense cutaneous diseases, from an anatomical 
standpoint, which have so modified a certain extent of the peri- 
phery as to fender absorption possible. 

Let me explain. If you have a patient affected with eczema, 
his skin is as if he had a blister. Under those conditions, he can 
absorb wonderfully well, and you should even exercise caution, 
for if too large a quantity of active principle is added to the bath 
poisoning may follow. Evident phenomena of absorption may 
also be manifested among women, chiefly among those who have 
extensive mucous surfaces, in whom the labia pudendi are 
largely developed. This surface is in itself sufficient to absorb 
active principles. Hence some reservations are to be made with 
regard to absorptions which may take place in a normal way 
with women, and accidentally with subjects affected with cuta- 
neous diseases. But as to arsenical baths for subjects affected 
with nodular rheumatism, absorption only takes place when the 
skin is more or less deprived of its normal epidermis. 

The use of substances dissolved in fatty bodies may be con- 
tinued without placing too much dependence upon their absorp- 
tion and diffusion. These may be facilitated by repeated and 
prolonged frictions, tending to render the deep-seated layers more 
permeable to active substances. This constitutes a method which 
was offered as a substitute to all others. With these mechanical 
processes may be included sinapisms and all rubefacient methods. 



148 PRINCIPLES AND METHODS OF THERAPEUTICS. 

With regard to gases and volatile principles, I have but to 
confirm what I have already said as to their facility of absorp- 
tion. This explains why extract of belladonna, applied on the 
abdomen, has shown marked effect upon the eyes, without the 
patient's hands having been instrumental in conveying it there. 
Compresses of chloroform also produce effects when covered over 
with impervious tissues to prevent evaporation. They not only 
have an immediate irritating, topical effect, but an eminently 
soothing, consecutive action, which shows that the chloroform 
has penetrated into the region, probably, by absorption. For 
this reason you may advise carbonic acid baths. Thus at Saint 
Alban and at Kissingen these baths have a marked influence on 
the skin. Carbonic acid first produces a very perceptible sting- 
ing sensation, then a reduction of sensitiveness, proportioned to 
the degree of local asphyxia. 

It is likewise because of this possible absorption that we so 
often make use of dry sulphurous, arsenical or mercurial fumiga- 
tions. These last have lately recovered the importance they had 
lost. They were formerly one of the methods most frequently 
used in cases of secondary syphilis, but they were abandoned be- 
cause of their difficulty. They are again in use, and without 
becoming a general method, will serve when circumstances forbid 
stomachic ingestion. 

Even by associating mercury with aromatics, we cannot guard 
against accidents with persons whose stomachs are rebellious, or 
those in whom diarrhoea sets in when they take a pill. The sub- 
jects being already poor in globules, we cannot allow them to 
sink under the influence of the remedy. In such cases, fumiga- 
tions are highly serviceable. They were formerly made with 
cinabar, and at present with calomel. Both methods, I believe, 
are good, even when there are no lesions on the skin, hence still 
better when those exist. For this reason favor has again been 
given to mercurial frictions, which were the exclusive method of 
certain practitioners of the last century. These frictions render 
great service ; they spare the digestive organs, and are remark- 
able for their decided and speedy effects. At times, a single 



CUTANEOUS METHODS. BATHS. 149 

friction is enough to produce symptoms of hydrargyrism, and to 
modify syphilis. However, neither this method nor any other 
can replace the use of mercurial preparations. 

The main objection to the cutaneous method is that the pro- 
cesses are often difficult to manage. It is easier to take a pill 
than a bath, and the ointments used are greasy and have a disa- 
greeable smell. But the advantages are often considerable. 
Those processes save the digestive organs, and in a certain num- 
ber of cases are prompt and safe in their effects, as we daily see 
in instances of syphilis. 



150 PKINCIPLES AND METHODS OF THEEAPEUTICS. 



CHAPTER XII, 
Diadermic Method —Hypodermic Method. 

Diadermic Method— History.— Mayer's hammer.— Ammoniacal ^blister.— Pre- 
cautions to be taken. — Its advantages and disadvantages. 
Entodermic Method — History. — The life-awakener. 
Hypodermic Method — History. 



Gentlemen : 

I have now reached the method to which I have given the 
name of diadermic or endermic. This consists in the introduc- 
tion of medicaments through the skin deprived of its epidermis, 
but otherwise unimpaired. Blisters, although unknown to Hip- 
pocrates and his immediate successors, have been in use a very 
loug time, and ever since the effects of vesical cantharidism have 
been observed, it is known that absorption beneath the epidermis 
is possible, since .the serous fluid takes up the cantharidine, and 
is afterwards absorbed through the surface of the denuded der- 
mis, thus conveying into the economy the active principles of 
cantharides, and giving rise to those very serious and often 
dangerous effects in the loins, known to us as nephritis and hem- 
aturia. These facts might have been observed a long time ago, 
but, in reality, the idea of reducing to a system the use of this 
method of absorption, belongs to Doctors Lambert and Lesueur, 
who, having combined their labors upon this new method, pub- 
lished their first results in 1823 (by Lesueur.) The endermic 
method received its name and full development in Doctor Lam- 
bert's work in 1828. In 1830 Gerard, of Philadelphia, who 
published the results of experiments made upon the leading sub- 
stances then in use — opium, belladonna, hemlock, nux-vomica, 



[diadermic method, hypodermic method. 151 



and many others used in the form of extracts or concentrated 
solutions, which he applied on the denuded dermis, had occasion 
to observe important physiological and therapeutic effects. But 
this method came into general use in 1833, after Trousseau and 
Bonnet published their work upon it, based upon cases in which 
morphine was used. From that date it assumed great import- 
ance in therapeutics, and I well remember the time when blister^, 
dusted over with morphine, were in as frequent use as hypo- 
dermic injections' of active substances are at present. 

Absorption by the endermic method is obtained by stripping 
the skin of its epidermis. For this purpose slow methods, like 
frictions, are to be discarded, but a blister is to be used. Still 
more expeditious processes are even preferable, if the physician 
desires to apply the remedy himself. Therefore, very active 
means of vesication are used. Cantharides might be employed 
when there is no urgency, but usually, preference is given to 
ammonia, or to Mayer's hammer, dipped in boiling water. 
Mayer's hammer, as so much used formerly, was at a temperature 
below 100°, and did not give rise to an eschar, but simply caused 
an ampulla. However, this process savored of barbarism, and 
no doubt the ammoniacal blister is in every respect preferable. 
Although this method has lost favor, yet it should not be entirely 
abandoned ; therefore I shall give you some details. 

The ammoniacal blister is prepared by the aid of what is called 
Gondret's ointment — (a mixture of lard and tallow, holding in 
solution the highly concentrated volatile alkali. There are two 
kinds ; one for winter, another for summer use.) Or else, as has 
been recommended, the blister is made by applying upon the spot 
a flannel pad, dipped in concentrated ammonia. A disk of agaric 
dipped in concentrated ammonia may also be used, but it should 
be covered over with a watch crystal, or something of the kind, 
for the purpose of isolating the part to be vesicated. Another 
very simple process, recommended by Trousseau, consists in the 
use of a sewing thimble, in which raw cotton impregnated with 
ammonia is placed. Raw cotton does not readily imbibe aqueous 
solutions. To overcome this resistance it should be washed in 



152 PRINCIPLES AND METHODS OF THERAPEUTICS. 

hot water, as Gayon advises, or better still, as I formerly showed, 
moistened with a very little glycerine, after which it will readily 
imbibe ammonia or any other liquid. The thimble containing 
the ammoniated cotton is then applied to the part to be vesicated, 
and maintained there for from three to five minutes, and some- 
times more. It may even require a quarter of an hour ; it de- 
pends upon the delicacy of the skin and the part which is being 
operated upon. With good ammonia, the delay of from three 
to five minutes will be found ample for almost all parts of the 
body. This may seem a short time, and the authors of the 
method favor a longer application. But it is not useful, and 
may be injurious. It is best to follow Trousseau's precept and 
remove the apparatus at the end of three minutes. No ampulla 
is formed, but the epidermis is more opaque, less smooth and 
somewhat wrinkled. This indicates that the operation is over, 
and it is needless to continue the application. The epidermis is 
detached and that is sufficient. When using very strong ammo- 
nia, if the application is continued too long it may produce an 
eschar, which would exclude absorption, since this takes place in 
an inverse direction from exhalation. If you give rise to exces- 
sive inflammation you create unfavorable conditions for absorp- 
tion. This applies equally well to small and large blisters. 

I shall never forget a poor fellow who was brought to the hos- 
pital suffering from cholera. He was not very ill, but he 
died from the effects of an ammoniacal blister of m .25 in di- 
ameter, applied upon him in town. The eschar had included 
not only the skin, but the underlying muscles. You see there 
are disadvantages and even danger in using ammonia on an ex- 
tensive surface. The apparatus must, therefore, be removed after 
from three or at most five minutes, and you will then notice that the 
skin is wrinkled. If this is the case, you remove it, because it 
is loose, and you have the denuded dermis, which is strewn with 
numberless little grooves caused by papillae, the hair follicles and 
the sebaceous glands. This surface, which is of a somewhat bright 
rose color, immediately exudes a large quantity of serous fluid. 

Before applying the morphine powder it is iudispensable to 



DIADERMIC METHOD. HYPODERMIC METHOD. 153 

wait until this secretion subsides, otherwise the patient would 
derive no benefit, as the serous flow would carry off the active 
substance. After a time, when the surface is simply moist, the 
substance may be applied. It is covered by a disk of impervious 
tissue, and secured by strips of diachylon. This forms the first 
dressing. 

There is a good cantharidized collodion prepared by a druggist 
in Lyons, which might be used to advantage. It produces vesi- 
cation only at the end of a few hoars, but it has the advantage 
of supplying its own dressing. Nothing is needed to protect it, 
hence its merits in the present question are self-evident. One 
the size of a twenty-franc piece could be applied, and after empty- 
ing the ampulla the active substance might be introduced as by 
inoculation ; it would be protected by the collodion cap and re- 
quire no further attention or dressing. Indeed, it might be used 
for fresh applications of the substance, because under the collo- 
dion the healing process is slower than in the open air. After 
this first operation there are precautions to be observed in order 
to secure absorption, for this method is either excellent or worth- 
less, according to the way in which it is used. 

When the second dressing is made, you will generally observe 
that the surface has changed its rose color to a grayish hue. Be- 
fore replacing fresh active substance the old should be removed, 
otherwise absorption will no longer take place. The substances 
employed vary according to the object desired. When the pur- 
pose is to obtain the absorption of a sufficient quantity of active 
substance through so small a surface, preference is, of course, 
given to what are called alkaloids, but, as even at the present 
day, all plants have not yet yielded for us their alkaloids, we 
have at times to use very impure substances, which resemble 
molasses, but which possess a certain amount of activity. 
When necessity requires, we may use these active substances, 
whose intensity of action is known to us, although they arc not 
absolutely pure. This method was formerly looked upon as pre- 
senting nothing but advantages. It however has a few draw- 
backs. It has the advantage of sparing the stomach, thus doing 



154 PRINCIPLES AND METHODS OF THERAPEUTICS. 

away with those rebellions which bring on vomiting, and the 
consequent loss of the active substance. 

By the endermic method, when you find that the effects pro- 
duced assume greater intensity than you contemplated, you have 
it in your power to reduce absorption, and even to remove any 
portion of the substance which has not yet acted. By washing 
off the surface you can prevent the penetration of any fresh por- 
tion of over active substance, which might give rise to phenomena, 
of intoxication, and you will presently see the value of this con- 
trol over accidents. Another advantage of this method is its 
greater activity and intensity of action over the stomachic way. 
I constantly dwell upon this point, because it is of great practi- 
cal importance. The stomach digests, that is to say, transforms 
everything introduced into it. Therefore medicaments given by 
way of the stomach only produce effects in the ratio of a third 
or a fifth of the bulk introduced. Consequently, if you intro- 
duce gr. 0.01 of morphine by the endermic method, you will 
obtain much greater effects than with a similar quantity by way 
of the stomach, yet gr. 0.01 is a medium dose for the stomach, 
and that usually used ; it about represents the amount of active 
principle in a spoonful of syrup of morphine, hence it is a fair 
dose, which may be rather heavy by the endermic method. 

I once attended a lady suffering intensely from ileo-lumbar 
neuralgia. I advised a small blister dusted over with morphine, 
which was obtained from the apothecary Mialhe. She made the 
first application of gr. 0.01 in the morning, then another at the 
end of the day, and the next morning she put on another centi- 
gramme. Hardly half an hour after this she was taken with 
most serious poisoning, and in a few moments was at the point 
of death. I arrived about that time and found her in a very 
alarming condition ; she was deathly pale, the pupils were 
greatly contracted, the somnolence amounted to coma, and she 
threw up all that was given to her. I thought she would die, 
but she recovered. As you may well understand, it was import- 
ant to stop absorption ; after having scourged her and adminis- 
tered coffee, I hastened to wash off the little blister, upon which 
there still remained some morphine. 



DIADERMIC METHOD. HYPODERMIC METHOD. 155 

As I have already stated, you see the advantage of being 
able to stay the effects of the substance. 

This great intensity of action is a disadvantage. But there 
are others which are only of importance to pusillanimous sub- 
jects. For example, all applications on the denuded dermis are 
painful, no matter whether the substance is soothing or irritating, 
it is all the same at first. The patient always complains of great 
pain. Even when you apply morphine upon a blister, the most 
masculine patient will yell. Women have greater courage. 
Still more so when other substances are used. The dermis is 
not intended for contact with irritating substances, while the 
stomach shows great tolerance, being accustomed to receive a 
little of everything. There are substances which, in the stomach 
only cause a slight stinging sensation, but when applied upon 
the dermis they produce a smarting pain, besides an increased 
secretion. Thus digitalis on the surface of the dermis may even 
give rise to small eschars. Those are the disadvantages. 

There are also cases in which absorption may fail ; this occurs 
Avhen the application has been made in too much haste, the 
secretions having carried off the active substance. 

In establishing a comparison between the hypodermic and 
endermic methods, we may say that the slight advantage in favor 
of the latter consists in the fact that unskilled hands may apply 
it. If need be, some member of the family may apply the 
powder. On the contrary, injections require a person possessed 
of some dexterity and practice in the art, or else the patient must 
have the courage of administering them to himself — which is rare. 
Hence it is almost always necessary for the physician to admin- 
ister the injections himself; this is not always convenient, as he 
cannot be present all the time. This is the only disadvantage 
possessed by the hypodermic method, and all that can be claimed 
over it by the endermic method. 

We have now to consider another way of introduction, 
called the entodermic method, which, although not used in 
a systematic way, may be employed in a certain number of 
cases. It was inaugurated in 1836 by Lefargue, of Saint Emi- 



156 PRINCIPLES AND METHODS OF THERAPEUTICS. 

lion, to whom it was suggested by the practice of vaccination. 
He concluded that medicaniental substances could be introduced 
by means of a lancet, the same as the vaccine virus. From a 
therapeutic point of view, the idea was old, for several centuries 
before him iElius had recommended the introduction of very 
active substances under the skin by the aid of some cutting 
instrument. This is the way Lafargue proceeded: he used a, 
lancet, on the extremity of which he deposited the active sub- 
stance reduced to a paste, that is, cemented by water or a solution 
of gum. He stuck the lancet into the region upon which he 
wanted to act. 

Another modification of this process consisted in introducing 
this same paste in the thickness of the dermis, but also in plac- 
ing under a watch crystal over the part, a concentrated solution 
of the active substance; there were thus two ways of introduc- 
ing the substance. The products inoculated were, in general, 
alkaloids, for quinine, morphine and atropine were already 
known, and these were the substances whose use was chiefly 
recommended. These inoculations were not only applied to pro- 
duce general effects; they were also used for the purpose of 
bringing on revulsion, and even the ulceration and the destruc- 
tion of the affected parts. Thus, for example, those vascular 
nsevi, so frequent in youth, which often disappear and as often 
increase in size (much to the despair of parents and child), have 
made physicians seek some way to secure their disappearance. 
]S T o doubt caustics may be employed, but they are disagreeable, 
hence more inoffensive, and apparently less alarming means have 
been tried ; among these, vaccination. This is what Lefargue 
practiced, only, in place of superficial vaccination, the lancet 
laden with vaccine matter was driven into the arterial or venous 
tissue. 

Inert substances have also been introduced for the purpose of 
developing an inflammatory process, and even croton oil has 
been inserted into those tumors. 

All these substances produce either a specific or ordinary 



DIADERMIC METHOD. HYPODERMIC METHOD. 157 

inflammation in such tumors, after which a cicatrix takes the 
place of the nsevus. 

As I said, Lafargue had the idea of using croton oil as an 
energetic revulsive agent. Applied upon the skin this oil deter- 
mines considerable irritation, and produces great effects. He 
thought its inoculation would determine still more powerful 
effects, and consequently lead to greater therapeutic results. 

That idea has been revived by a Westphalian veterinary sur- 
geon, who has derived from it a process which he applies to all 
cases; he has even invented an instrument which he calls a llfe- 
awakener (Lebenwecker.) This instrument consists in a tube 
containing a spiral spring around a rod bearing at its end needles 
stuck in a little leaden cushion. After applying the apparatus 
on the skin, the rod is drawn back, then allowed to spring. The 
needles, forming a sort of biush, penetrate into the skin, and as 
they have been dipped in croton oil, they represent so many 
little inoculations made with a lancet. In this way the oil is 
carried to a considerable depth, and excites a very decided irri- 
tation. But this process certainly does not deserve being ranked 
as a doctrine, as is being done in Germany. 

I now come to the hypodermic method, that is, to one of the 
greatest acquisitions of modern therapeutics. It is the most 
perfect way by which to insure and measure the effects of medica- 
ments. It is, therefore, the best method, from a practical stand- 
point, and also for the purpose of interpreting phenomena, 
because nothing is more important, when conclusions are to be 
drawn, than to be certain of what has been done. With the 
stomachic, endermic and respiratory methods, we are never cer- 
tain of having introduced all that we wanted to introduce, and 
consequently we cannot measure the phenomena according to 
their cause. With the hypodermic we can safely do so, because 
we are sure of what we introduce ; the results must be in pro- 
portion to what has been introduced, because there is no loss and 
no destructive causes. We here have convincing elements which 
exist in no other method ; this gives you the extent of its im- 
portance. 



158 PRINCIPLES AND METHODS OF THEAPEUTICS. 

So far as I know, the first idea of the hypodermic method 
suo-o-ested itself to Fourcroy, the illustrious chemist, who did so 

too J ' 

much for medical science. 

In 1785, he suggested introducing under the skin, in the 
lamellar tissue (it has changed its name), active substances which 
would there find all the conditions for integral absorption and 
the fullest development of all the effects of which they were 
capable. In support of his theory he pointed to experiments 
which had already been made upon animals, in whom tepid 
water, emetics and purgatives had been introduced and followed, 
in some cases, by their effects. The reason Fourcroy's idea was 
neglected is, that during his lifetime, and afterwards, the greatest 
dread existed with regard to introducing active substances into the 
circulatory system. This fear was not altogether unwarranted, 
it had some grounds for existence ; but this accident happens 
but once in thousands of injections, hence it should not pre- 
vent us from using a method which is the best among all ; 
besides, by observing a few precautions, it is possible to guard 
against the introduction of substances into the venous system. 
Anyhow, for a long time active substances have been introduced 
into the sub-cutaneous cellular tissue, only in a different way 
from that practiced at present. 

There were two processes chiefly used by veterinary surgeons : 
a wide wound was made into the skin, into which a sharp instru- 
ment was introduced for the purpose of cutting the lamels of 
the cellular tissue, and after an artificial cavity had been formed, 
the active substances were introduced. 

Langenbeck conceived the idea of modifying Lefargue's pro- 
cess, by proposing to insert the lancet below the dermis. Then, 
by slightly turning the instrument in the wound, allowing the 
substance to slip in, it was then possible to deposit it in the 
elements of the sub cutaneous layer. 

These were the two processes, to which two others may 
be joined. 

One belonging to Trousseau, which I have frequently seen 
him use, and which has given some good results. Having ex- 



DIADERMIC METHOD. HYPODERMIC METHOD. 159 

hausted every device for soothing sciatic pains, he one day con- 
ceived the idea of introducing sedative substances in close prox- 
imity with the point of emergence of the sciatic nerve. For this 
purpose he practiced a rather wide incision of from m .01 to m 
.015, and carried it through the whole thickness of the skin to the 
deep fascia superficialis. He then placed there a large pill con- 
taining, among other things, gr. 0.10 extract of belladonna, and 
as much opium. At that depth dissolution took place slowly; 
there was a constant supply of narcotic principle, which, in a 
number of cases, calmed stubborn sciaticas. 

He also made use of another process, called inoculation par 
enchevillement : after having made a puncture with the lancet, he 
followed the section of the skin, and introduced into the cavity 
thus created, a sort of troche, (similar to a rectal suppository,) 
which contained a certain proportion of active principle. That 
formed a kind of wedge — (cheville.) 

All those processes are barbarous ; we now have a much more 
elegant and far better method. 



160 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XIV. 
Hypodermic Injections. 

History [continued]. — Substances that can be injected. 

Injection Syringes. 

Alkaloids and Glycosides— Cmara.— Mineral sal's. — Nutrient substances. — 
Serum in the blood. — Peptones. 

Physical Requirements for Injections — Solubility .—Water. — Alcohol.— Glycerin e. 

Chemical Requirements for Injections — Effects of acids. — Greater solubility of 
salts. — Exceptions. 

Effects of Alkalies — Correctives. — Albumen. — Hydrobromic acid. 

Standards of Solutions — Injections of one-fifth: Ergotine, quinine, quinoidine. 
Injections of one-tenth : Curara, conin, conicine. Injections of a fiftieth : 
Morphine, veratrine, strychnine. Injections of a five-hundredth: Atro- 
pine, duboisine, daturine, nicotine, eserine and aconitine. 



Gentlemen : 

The era of the hypodermic method oegins at that date of 
1845-46 when Pravaz, of Lyons, imagined the introduction of a 
more or less concentrated solution of perchloride of iron in cases 
of anseurism, so as to cause a coagulation of the blood and thus 
heal the tumor. It is true that in 1844 an attempt of this kind 
seems to have been made in Dublin ; that is, an endeavor, was 
made to introduce a medicinal substance under the skin. But in 
reality, it was only in 1853 that the real hypodermic method was 
invented by Alexander Wood, of Edinburgh. 

He made use of Pravaz' syringe to introduce active substances 
under the skin, and he naturally premised by the use of mor- 
phine. He found imitators among a number of progressive men, 
among others, Charles Hunter, in England ; Behier and Courty, 
in France, and Von Grsefe, in Germany. 

At present this method is in general use, and is still growing 



HYPODERMIC INJECTIONS. 161 

in favor, and we should invariably avail ourselves of it whenever 
we can. 

The substances at present used already make up a long list. 
Morphine was first injected by Alexander Wood ; atropine is in 
constant use as an adjuvant to morphine in determining stupor, 
or else as an antagonist of that substance ; aconitine, of which I 
was the original user, first, that prepared by Hottot, then Duques- 
nel's, which is purer; quinine, which has often been injected under 
the skin, and has been found serviceable, although there are many 
disadvantages in thus employing it ; then again, and without any 
drawbacks, the hydrobromate of quinine and of cinchonidine ; 
also curara, which Vella, of Turin, employed, as well as Claude 
Bernard jl I have myself used picrotoxine and digitaline; ergo- 
tine has recently been exhibited in injections very much as I had 
used it in 1874, in an affection of the venous system, due to an 
obliteration of the descending vena cava. At present, we not 
only can use Bonjean's ergotine, but ergotinine. Some years 
ago the introduction of mercury under the skin was deemed de- 
sirable. Finally, within a recent date, ether, chloroform and 
emetine have been injected, and I have myself done so, after Dr. 
Ornella's experiments upon animals. I shall not speak of tartar 
emetic and croton oil, both of which have been recently men- 
tioned. But as you see, there are at present a great number of 
substances used. Progress is in the direction of this method, 
which can but increase in usefulness, especially in nosocomial 
establishments, where doses may be much more easily repeated 
than in private practice, which is necessarily disseminated. 

I have given you a general indication of the many circum- 
stances in which the method can be resorted to. Let us now 
look into its details, and first of all, the instrument required. 
This consists of a syringe, to which different forms have been 
given. At first, such was the fear of too high doses, that a 
syringe was invented, the piston-rod of which, in the form of an 
endless screw, worked in a screw-thread in the cap of the glass 

1 CI. Bernard. Lessons on the Effects of Toxical and Medicamental 

Substances. Paris, 1857. Experimental Science, (2d ed.) Paris, 1878. 

L 



162 PRINCIPLES AND METHODS OF THERAPEUTICS. 

cylinder. Each half turn represented a drop, and as many half 
turns were made as there were drops of active substance to be in- 
troduced. This was a defective process, and I never would em- 
ploy it, although at one time no other syringe was sold, either in 
England or elsewhere. I had Luer make me an ordinary 
syringe, working by pressure. He only added a sort of gauge 
on the graduated rod, by the aid of which it is possible to de- 
termine in advance when the introduction of the remedy is to 
stop. This is by far the most preferable way. 

When an active liquid is to be introduced by means of the 
turn-screw, it often happens that one forgets whether half or full 
turns have been made, hence this is is a frequent cause of error. 
Besides, when you are obliged to hold the syringe and turn the 
screw you have to drop your hold of the skin, the needle some- 
times comes out, or the liquid is spilled. In fact, difficulties of 
all kinds attend you. 

On the contrary, when the syringe is held in the right hand, 
between the thumb and medius, the index pressing on the piston, 
one hand remains free to hold the fold of the skin, and no un- 
easiness need be felt as to the quantity of active substance intro- 
duced. This is evidently the best process, and no one at present 
uses the old style of syringe. 

The substances employed are chiefly alkaloids, and it may be 
said, in a general way, that the remedies should be the purest 
active principles of the medicaments in use — the quintessences 
of Paracelsus. Immediate active principles are divisible into 
two principal categories : alkaloids and glucosides. But alka- 
loids are almost invariably used, even in the case of curara, for, 
notwithstanding the doubts which have been entertained as to their 
composition, what appears the active principle in this substance, 
which I believe to be derived from strychnine, is the methyl and 
the ethylo-strychnium, for the effects of these last are so very 
similar to those of curara that they may be considered identical 
in effects with curara and curarine. 

At times, mineral salts are injected. I shall not mention 
emetine, because, as I previously observed, it is not a real agent 



HYPODERMIC INJECTIONS. 163 

of the hypodermic method ; it can only be used as an irritant, 
and to produce a deep eschar; that is, in the method extolled by 
Luton. 1 

But we have all the salts of mercury which have been and still 
are very frequently used by a certain number of practitioners; 
also, the ethereal liquids, like ether itself, and chloroform, which 
have but lately been thus introduced. There is also croton oil, 
which I mention, but which is not to be used ; and some have 
injected alimentary liquids. 

Thus, in cases when the stomach is unable to perform digestive 
labor, or in constrictions of the oesophagus, also in a number of 
other circumstances, it has been suggested to introduce nutrient 
substances under the skin. This would not be a way of keeping 
up strength, nutrition and life, but it would at least enable us to 
stave off the fatal issue. For this purpose various substances 
may be introduced, for example, broth, provided it is divested of 
all fat. But I might as well here tell you that broth is a very 
delusive aliment; it is more a condiment, capable of exciting the 
stomach, and it is by an error that it has been classed with pep- 
togenic articles. Milk and the serum of blood can also be thrown 
in. Peptones might also be injected ; that is, substances obtained 
by the action of pepsine, either upon the fibrinous matter of the 
blood or on albumen, or on the nitrogenized matter of the mus- 
cles. But these peptones would have to be freed from any excess 
of pepsine, as this ferment would exercise its action just as well 
on the cellular tissue as upon substances submitted to its digestive 
effects. Upon the whole, notwithstanding what has been said, 
no great reliance is to be placed upon hypodermic injections of 
alimentary substances. 

Liquid substances can, of course, be introduced under the skin. 
This lias been done with ether and chloroform. Although these 
experiments have not been fully successful, yet, in a certain 
number of cases, sedative effects might be obtained in neuralgias 
and general pains. But solid substances must be dissolved, and 
this, as far as practicable, should be done in water. Most of the 

1 Luton. Treatise on Subcutaneous Injections. Paris, 1875. 



164 PRINCIPLES AND METHODS OF THERAPEUTICS. 

alkaloids are soluble in water, but unfortunately, in some in- 
stances, not sufficiently so, hence the addition of more powerful sol- 
vents becomes necessary. Of these I shall only name a few. 
Alcohol is often used. Chloroform has been recommended, but 
it is irritating, although later experiments show less of this 
feature. Glycerine has been employed. It has been used for 
dividing calomel, and allowing its introduction by the aid of 
Pravaz's syringe. Mr. Constantin Paul has even suggested the 
use of glycerine as a general solvent. It is no doubt a good dis- 
solving agent for a great many substances, but it is a polyatomic 
alcohol, and when used pure or insufficiently diluted it causes an 
irritation of greater intensity than that which the active sub- 
stance itself would produce. A solution of creosote has even 
been proposed. I am really at a loss to say why. Acids and 
alkaline salts have been used as adjuvant agents with metallic 
salts. Many of these solvents, such as alcohol and chloroform, 
are highly irritating, hence they should be used in as small quan- 
tities as possible. Injections of distilled water would no doubt 
be the best, but, as I remarked, there are many substances which, 
being insoluble in water, have to be made soluble by the addition 
of substances that are often slightly irritating. As to alcohol, it 
can be used in rather considerable proportions. Thus, at my 
outset, in order to obtain a solution of one-sixth in strength of 
mono-bromhydrate of quinine, I have sometimes used from 2 to 
3 parts of alcohol to 10 of vehicle. Even with this rela- 
tively considerable proportion, I had no particularly irritating 
effects, but simply the production of a little heat. 

All my students can bear witness that even with this solution 
of mono-bromhydrate of quinine an intense irritation is never 
produced in the region where the injection has been given. At 
most, a little induration is manifested, but usually no trace is 
even seen of where the injection was made. Therefore, if 3 
grammes of alcohol in ten do not produce irritating effects, we 
should not be over-distrustful as to the topical effects attending 
these adjuvants of water. However, if much more was added, 
considerable irritation would follow, and even an eschar might 
be formed. 



HYPODERMIC INJECTIONS. 165 

Thus eschars have been produced by pure alcohol used in dis- 
solving quinine. It is true this occurred with a cholera patient, 
who was vomiting everything; unable to obtain a sufficiently 
concentrated solution in any other way, I used pure alcohol. In 
this case the tissues were so very dry that the injection produced 
a small superficial eschar. Alcohol as a dissolving agent is best 
adapted to alkaloids. This is readily explained by the fact that 
dissolution is generally effected between proximate substances, 
while combinations usually take place between dissimilar sub- 
stances. Alcohol is comparatively a proximate of the alkaloids; 
besides alkaloids are proximates to fatty substances, and these 
are soluble in alcohol, therefore it is by alcohol that fatty sub- 
stances and resinoids may be dissolved. 

Acids may be used to facilitate the dissolving of metals, also 
to increase the solubility of neutral salts, these being less soluble 
than acid salts. Hence when acid is added to a neutral salt, its 
solubility is increased. Therefore this is still more the case when 
acid is added to an oxide or to a metal. As an example, take 
calomel, which is insoluble. If the protochloride is trans- 
formed into a bichloride, the result is a soluble salt. Likewise 
if you add enough acid to mercury, so as to render it soluble, 
you can introduce it by the hypodermic method. The same ob- 
servation applies to a great many organic substances. Strychnine 
is insoluble, but its salts are soluble; atropine is hardly, while 
its sulphate is very soluble. The chlorhydrate of morphine is 
six or eight times more soluble than morphine. Hence, you see, 
the addition of an acid is a means of promoting solubility. 

There are instances, however, where this is not the case. Caf- 
feine, for example, is not any more soluble when in combination, 
than when free, but this is an exception. Neutral sulphate of 
quinine is but very slightly soluble, requiring 740 parts of water ; 
hence, it takes 740 grammes of water to dissolve one gramme, 
while the acid sulphate of quinine is soluble in 11 parts of 
water. Consequently, bi-sulphate of quinine, obtained by a 
different process, is always used. 

It is generally believed that to obtain bi-sulphate of quinine, 
it is necessary to add a powerful acid, like sulphuric acid, to the 



1G6 PRINCIPLES AND METHODS OF THERAPEUTICS. 

neutral sulphate. This is not the case • a weak acid will answer 
as well. It will combine with a portion of the base, and an 
acid sulphate will be the result, since all of the sulphuric acid 
will now only be combined with a portion, while, at first, it was 
united to the whole of the base. 

In this way CI. Bernard was able to obtain a solution of a 
twelfth by the addition of tartaric acid ; citric acid would answer 
equally well, and increase the solubility of neutral sulphate of 
quinine in the proportion of 11 to 740. 

Alkaline salts, like the chlorides of potassium and iodine, 
possess the faculty of combining with analogous salts of mer- 
cury and copper, and thus forming double salts, in which they 
occupy the place of bases. Thus with chloride of sodium and 
proto-chloride of mercury there is formed a proto-chloride of 
mercury and sodium. These salts, of more complex composi- 
tion, are far more soluble than the first. ' Chloride of potassium 
is therefore added to the salts of the last sections for the pur- 
pose of making sub-cutaneous injections with more concentrated 
solutions. 

Besides these adjuvants, we should use correctives. In addi- 
tion to having a good solution, we must bear in mind that active 
substances are possessed of highly irritating qualities ; this is the 
case with mercurial salts. When even small proportions are 
introduced, they give rise to little phlegmons and furuncles, and 
even, in some cases, to gangrene. It would be discouraging if 
these accidents were of frequent occurrence. Mercurial salts 
have been combined with albumen. Other albuminoid sub- 
stances, like gluten and legumine, might be used. To obtain 
that result, the bi-chloride is added to an albuminous solution. 
Here we have to note a very interesting chemical peculiarity, 
because it illustrates how certain substances are incorporated : an 
albuminate of proto or bi-chloride is formed, according to the 
salts used, and under this form metallic substances lose almost 
the whole of their nocent qualities. 

These are the corrections chiefly used. Abroad, in Vienna, 






HYPODERMIC INJECTIONS. 167 

for example, these injections are much used. They offer some 
advantages, hence should be kept in mind. 

Quinine has also its corrective. "When the alkaloids from 
cinchona are combined with bromo-hydric acid, they lose all 
their irritating character. I noticed this immediately some 
years ago when I first used injections of bromo-hydrate of qui- 
nine. Whenever they gave rise to a slight suppuration, it was 
either because the injection had been given by a novice, who 
had made a sort of tunnel within the thickness of the dermis, or 
else because the general sanitary conditions were such that any 
slight wound would induce suppuration. 

That is what happens with tuberculous patients. In certain 
cases I tried with them injecting bromo-hydrate of quinine for 
the purpose of reducing their afternoon fever, and that occasion- 
ally caused abcesses. But these accidents are rare, and I may 
say that, among thousands of injections, I have only had five or 
six cases in which abcesses have formed. 

Bromo-hydric acid is not only a corrective of quinine, but like- 
wise of all alkaloids of cinchona. Thus, I have lately made 
extensive use of injections of bromo-hydrate of cinchonidine, 
because certain cinchonas from Sumatra and the East Indies, 
yield a large quantity of this substance. 

When the cinchona succirubra was first cultivated in those 
countries, it was discovered to chiefly yield cinchonine ; the local 
physicians found that good results were obtained with it, and 
being anxious to learn if injections would be harmless, I tried 
some, and satisfied myself that such was the case. I have at 
present in my hospital service, a number of patients upon who n 
no visible traces of injections can be found ; all that indicates the 
places is simply what resembles a flea-bite. I have likewise 
made injections with what is called quinetum. This name has 
been given to the whole of the alkaloids supplied by the cin- 
chonas grown in the East Indies. We are becoming so poor in 
cinchona, that we have to make good use of everything. These 
combined bromo-hydrates are as inoffensive as those of cinchona 
and of quinine. 



168 PRINCIPLES AND METHODS OF THERAPEUTICS. 

I have also made use of what is called quinoidine. This is 
what remains after cinchona bark has been so treated as to ex- 
tract from it all the crystal lizable alkaloids. It is a brownish 
residuum ; I have injected it, and from it I have obtained 
comparatively good results. No doubt these effects could not be 
compared with those of the alkaloids as tonics and moderators of 
fever, but the injections I made were attended with no evil results, 
although I had but little confidence in the substance used, because 
of its rather dark color, and the fact that it is not limpid. 

This shows that bromo-hydric acid, when in combination, seems 
to correct those irritating properties which, for a long time, had 
caused the use of these alkaloids to be abandoned in the hypo- 
dermic method. It is indispensable to use only standard solu- 
tions ; were these made ad libitum you would never know the 
strength of the agent used. There is, moreover, a moral and 
material Obligation in not using more than one syringeful at each 
time, that is, a dose must be contained within a cubic centimetre. 
A repetition of the puncture is a repetition of the pain, with a 
timid subject. Besides, if the treatment is to continue, you 
would soon no longer find an unpunctured spot on the skin. 
The syringe is but of small capacity. It only contains a gramme 
of distilled water ; and it is well you should know that all 
syringes are of the same calibre. 

Since the syringe only contains a cubic centimetre of distilled 
water, it is necessary to introduce into it a sufficiently active dose 
of medicament • for example, 20 centigrammes of bromo- 
hydrate of quinine, or 2 milligrammes of atropine. We dis- 
tinguish 4 degrees of concentration in the solutions used for 
injections, and as these standards seem to answer all the require- 
ments, I beg you will bear them in mind. 

In the first place, we have very massive solutions, like those 
of ergotine, of bromo-hydrate of quinine, and of cinchonine, 
which are made in the proportion of a fifth, because we cannot go 
beyond that, however desirable it may be, owing to the solubility 
of those salts. Bonjean's ergotine is soluble in a fifth and even a 
fourth. A syringeful will contain from 20 to 25 centigrammes. 



HYPODERMIC INJECTIONS. 169 

There are rather less dense solutions of a tenth, like those of 
curara; no doubt curarine would be desirable, but we have not 
got it. In these solutions of a tenth, there are 10 centigrammes 
in a cubic centimetre of water, as in the case of the conin and 
conicine prepared by Mourrut, which I have injected under the 
skin without obtaining any great physiological action. 

Next come the solutions in most general use — those of a fiftieth ; 
that is, 2 centigrammes in a syringeful of 1 gramme. These 
are solutions of morphine, veratrine and strychnine ; that is, 
alkaloids that are used by centigrammes, or half centigrammes. 
These solutions are at present very much used, hence it is well 
you should remember this standard of a fiftieth. 

Use is likewise made of solutions ten times weaker ; that is, at 
a five-hundredth, for substances whose activity is formidable, 
like atropine, duboisine, daturine and nicotine, which have been in 
use for a number of years; also eserine, and finally, aconitine, 
which is the most powerful alkaloid I know of, since its poison- 
ous effects can show themselves with doses of 1J milligrammes. 
These solutions can be used in concentrations of a five-hundredth, 
because you have 2 milligrammes in a syringeful, and it is 
always easy to divide by eye-measure this capacity into two or 
four portions. You then have doses of 1 milligramme, or of 
half a milligramme, of active substance. 



170 PKINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XV. 
Hypodermic Injections— [ Continued.] 

On the Choice of a Region— Tolerance of certain regions.— Facility for absorp- 
tion. 
Injection loco dolenti — Special regions. 
Manner of Operating. 

Solution — Its standard ; its concentration. — Algse. — Their effect. 
Preventive Methods against the Development of Algoz. 
Local Effects of Injections. 



Gentlemen : 

Now that you are acquainted with the instrument, and that 
you know the standards of the solutions, let us consider the selec- 
tion of a region. 

Several considerations are here to be observed. If our only 
object is to secure, in the easiest possible way, the absorption of 
an active substance, from which we only expect generalized effects, 
we shall choose that region which is most accessible and most ab- 
solutely favorable to absorption and its subsequent results. 

Guiding ourselves by this absolute statement, we must select a 
region which is usually covered. With women, injections should 
never be made in the upper part of the chest. We must choose 
a region over which the skin is soft, easily separated from the 
subjacent parts, and in which a fold is readily made ; conse- 
quently, that region must be underlaid by a somewhat loose and 
elastic cellular tissue. I do not mean a filamentous tissue, be- 
cause injections are never successful in such tissues ; they give 
rise to more or less active inflammations, as is the case on the 
dorsal surface of the hand when it is thin. 



HYPODERMIC INJECTIONS. 171 

The case would be similar with the eye-lids, the scrotum, and 
rtgions where the cellular tissue is lax. As far as practicable, we 
must select regions possessed of considerable vascularity, and not 
of excessive sensibility. Extended vascularity favors rapid ab- 
sorption, while excess of sensibility predisposes to inflammatory 
developments. There are a number of regions which possess all 
the foregoing conditions. What I have said can be of no in- 
terest to those who believe that absorption takes place equally 
well in all localities, and that selection is simply for the purpose 
of convenience. Thus there is a foreign physician who believes 
that a substance can be placed indifferently in all regions. But 
all careful observers hold an opposite opinion, and this is so well 
grounded that an attempt has been made to establish a scale of 
absorbing qualities from the region which absorbs best to that 
which absorbs least. It has been thus arranged : 

1st. The temples and the cheeks. 

2d. The hypogastric region. 

3d. The front of the thorax. 

4th. Supra and sub-clavicular region. 

5th. The internal face of the arm and of the thigh. 

6th. The nape of the neck. 

7th. The external part of the thigh. 

8th. The external part of the arm. 

9th. The forearm. 

10th. The leg. 

11th. The foot. 

12th. The back. 

This distribution would lead us to conclude that the more cen- 
tral the regions the better does absorption take place, and that as 
we approach the periphery we notice a reduction in the absorb- 
ing faculties of the subcutaneous cellular tissue. 

I have some reservations to make in regard to this method of 
graduating the absorbing powers. No precautions seem to have 
been taken against one of the causes of error most frequently 
met with. I have reference to the fact that when an injection is 
made upon a region separated from the skin by but a trifling 



172 PRINCIPLES AND METHODS OF THERAPEUTICS. 

space, diffusion may give rise to phenomena which bear the ap- 
pearance of having been caused by* prior absorption and convey- 
ance through the circulation. Let me explain. If you wish to 
ascertain whether a substance produces tetanic effects upon a frog, 
you give it a subcutaneous injection, but you must carefully avoid 
all proximity to the vertebral column, otherwise phenomena will 
be produced simply through imbibition of the tissue, and a trans- 
fer of the substance in contact with the marrow. 

Under these conditions, what you obtain with a convulsive 
agent you would also have with chloroform or chloral and all 
substances capable of exercising an irritating influence upon the 
spinal centre. 

When I see the temporal region indicated as that which ab- 
sorbs best, of all, the experiments generally having been made 
with atropine, I am inclined to think that in a number of cases 
mydriasis was caused more by the diffusion of the active substance 
than by extra rapid absorption. 

Rather subtle distinctions are also made : for example, when 
we are told that absorption is more rapid on the external face of 
the thigh than on the external face of the arm, I must say that, 
although I have made very many experiments, I have never 
noticed such differences. 

I must admit, however, that there are regions which absorb 
more readily than others, and they are precisely those which cor- 
respond with the direction of flexion, and in which vasculariza- 
tion is greater and temperature higher. 

My conclusion therefore is, that but few regions possess the 
desired conditions of great facility for operative mechanism, and 
a skin which is easily folded — that is to say, superposed over a 
layer of lax and pliant cellular tissue, besides being a region in 
which irritability is not very great. The best among these 
regions are the waist and the abdomen. With these you are al- 
most sure never to have accidents, and you can depend upon in- 
tegral and rapid absorption. 

Another object we should endeavor to secure is the most abso- 
lute tolerance for all irritating substances. In fact, there are a 



HYPODERMIC INJECTIONS. 173 

number of raedicamental substances which, when introduced into 
the cellular tissue, are to a certain extent irritating, no matter 
what precautions may be taken, even if the ingredients are com- 
bined with albuminoidal substances. Thus mercurial salts retain 
their highly irritating qualities in many circumstances, and in 
spite of all precautions it is impossible to avoid inflammatory 
nodules, and sometimes even furunculous abcesses. In these cases 
we must select the most tolerant region, and that is the back, be- 
tween the two shoulder blades. The skin there easily makes a 
large fold, and besides, the region is but slightly sensitive. This 
should always be a guide in the matter of injections. Injec- 
tions with mercurial salts maybe made in this region with hardly 
any inconveniences. 

Therefore, if you only desire facility of absorption and oper- 
ation you will select the waist. If, on the other hand, highly 
irritating substances are to be tolerated, you will choose the back. 

At times, another object is to be attained. It is desirable to 
act in a predominant manner over an organ or an apparatus, and 
for that purpose the active substance is deposited in as close prox- 
imity as possible to the region or the organ which is to be mod- 
ified. But the geometrically shortest road is not always the best. 
There are circuitous ways which can be taken for the purpose of 
rapidly and energetically modifying a part. In general, when 
we desire to allay a pain, we bring the narcotic or stupefactive 
substance into the neighborhood of the painful region. In cases 
of sciatica, it is below the gluteal fold that we place the substance, 
because between it and the nerve the distance is not very great, 
geometrically speaking. This proves quite successful in those 
cases. That is a condition we must endeavor to realize whenever 
we desire to obtain the most extensive possible therapeutic effects 
upon parts affected either with convulsions or spasms. 

But there are other circumstances, as I stated before, in which 
we can keep far away from the region to be modified, provided 
the region upon which the remedial application is made is in an- 
atomical connection with the region to be acted upon. For ex- 
ample, when we wish to act upon the heart, we of course know 



174 PRINCIPLES AND METHODS OF THERAPEUTICS. 

that it beats in the fifth intercostal space, and under the adjacent 
parts ; it would, therefore, be natural to apply the active sub- 
stances there. But we must not lose sight of another consider- 
ation, which is the vascular connections between the region and 
the heart itself. 

These connections are in the epigastric depression. This has 
been demonstrated by an army surgeon. It is also in this region 
that substances should be applied, when intended to act upon the 
bulb of the aorta, for it has been proven by physiologists that 
there exists an intimate connection, from a functional point of 
view, between the epigastric region and the bulb, and that when 
it is necessary to act upon the bulb, so as to annul its functions, 
for the purpose of putting an end to syncope, it is there we must 
address our efforts. If, for example, you are called upon to 
attend persons laboring under collapse, caused by an excess of 
chloroform, it is upon that region that you are to bring all revul- 
sives to bear, and chiefly electricity. The same may be said of 
medicamental substances to be introduced under the skin, for the 
purpose of acting upon the bulb itself. 

Thus, you see, there are cases where, on account of functional 
relations between distant regions, it is upon the connecting region 
that medicamental action is to be directed. 

But what I have just said supposes the existence of a maxi- 
mum action more powerful than that upon the whole system, and 
exerted around the region itself, in which the active substance 
has been introduced. I shall prove this to be the case. Al- 
though a number of able men have supposed that medicaments 
deposited under the skin act only after absorption, it is, however, 
evident, from an attentive study of all the facts, that there is con- 
siderable topical action, and that the nearer you approach the 
affected region the more favorable will be the results obtained. 
No doubt injection is the best method of carrying, with the 
shortest possible delay, the largest quantity of active principle 
into the circulation, but from this it does not follow that topical 
action does not preponderate. 

Let us now consider the operative process we must follow in 



HYPODERMIC INJECTIONS. 175 

order to be successful. You mu«t not believe that Wood's little 
operation is as simple as might be supposed from the instrument, 
and the apparent absence of obstacles in the way of medica- 
mental substances. There are difficulties with which you must 
be made acquainted. 

In the first place, there are some precautions to be observed 
prior to the operation ; these relate to the instrument, the solution, 
and the subject. With regard to the instrument, an indispensable 
precaution is to ascertain each time that the piston closes prop- 
erly, and that the needle is not stopped up ; this will save 
unpleasant mishaps when you are at work. Besides, each time 
you practice an operation upon patients liable to impart conta- 
gion, you must be careful, as Mr. Pasteur advises, to wash the 
instrument with alcohol. You know that syphilis is wonder- 
fully well transmitted by vaccination. The fact of this knowl- 
edge should put you on your guard against the use of an 
unwashed needle. Of not less importance is this when you 
operate upon persons affected with a serious and contaging dis- 
ease, like diphtheria. 

Precautions are to be observed with regard to the solution. 
The active substance must, of course, be of good quality ; I have 
told you why the solution should be a standard one, and the 
standard must not be too high. It often happens that, although 
substances have been well dissolved at the time of their intro- 
duction into the liquid which is to serve as their vehicle, yet, on 
account of its being a saturated solution, crystals are formed 
after a given time. 

In other words, a solution is simply a division into the 
molecular state, as is the case with the fi brine of- the blood serum, 
or else with the phosphates in the urine, which becomes clouded, 
because the molecules of phosphates and carbonates, which were 
in a state of extreme and indivisible division, finally unite and 
form a molecule which is precipitated, or else floats and forms 
that prismatic film known by the name of fatty urinal coating. 

Something analogous happens in the solutions, especially if 
they have been prepared at a higher temperature than they after 



176 PRINCIPLES AND METHODS OF THERAPEUTICS. 

wards possess. This precipitation has more than one disadvan- 
tage. The standard of the solution is reduced, and this does 
not only take place according to the co-efficient of solubility pre- 
sented by the active substance at different thermometrieal 
degrees. You might suppose that if at a temperature of + 20°, 
it is soluble in the proportion of a tenth, and at -{-15°, of a 
ninth, that it is one-ninth of the substance which has disappeared 
and that it is only necessary to filter it. But that is not all. 
Physicists and chemists know that when a saturated solution has 
allowed crystals to separate, what remains of the solution is of a 
lower standard than that indicated by theory. In other words, 
when crystals are precipitated they carry with them a certain 
proportion of the substance which should have remained in solu- 
tion. 

Again, there is the danger that a detached crystal may find 
its way into the syringe ; this happened to me once ; the crystal 
stopped up the needle, and as I continued pressing upon the 
piston, the canula separated from the pump barrel, and all the 
solution was spilled. Besides, when a crystal has passed through 
and is introduced under the skin, it acts the part of a thorn, and 
not only by its mechanical action, but in its capacity as a chemi- 
cal body, it gives rise to a number of inconveniences which we 
shall in due time consider. 

The solution must be carefully preserved, and in connection 
with this there are interesting points deserving your attention. 
After a time all hypodermic solutions become turbid ; this is not 
clue to a precipitation of active substance, but to the presence, 
first of spores, then of simple filaments, which finally ramify 
and which are formed by a low order of vegetation belonging to 
the genus leptomitus. They are filamentous algce, which might 
also be called mucedines ; but the distinction, to my mind, is of 
but little importance, as I never could see any difference between 
a mucedo and an alga. The difference is said to consist in the 
coloring matters, in the one ; but the same plant will show a 
green color if exposed to light. Thus the sidpuraria, of which 
I spoke, is colorless at the origin of springs, or when it grows 



HYPODERMIC INJECTIONS. 177 

in dark passages, but it assumes a beautiful emerald green when 
it vegetates in the light. I therefore call them all algoe, because 
they live in water. 

These algae develop in a rapid and, in one sense, destructive 
manner in all solutions which have stood for some time. They 
cause the disappearance of a certain quantity of the active sub- 
stance, and, besides, act the part of foreign bodies. I need not 
insist upon the inconveniences they thus present, but what I 
said with regard to crystals applies with still greater force to veg- 
etable substances which are not so easily destroyed. Another 
circumstance is, that they greatly reduce the strength of the solu- 
tion to be used. I was the first to call attention to the presence 
of these algae in hypodermic solutions; and I advanced the 
opinion to which I still adhere, that they withdraw a portion of 
the active substance from the solution, because that substance 
contains nitrogen, and alga, like all young vegetable cells, 
requires a nitrogenized substance upon which to develop. Hipp. 
Bourdon has called attention to another effect of these algae. As 
you are aware, filaments and pointed substances form a centre of 
attraction for all substances that have a tendency to separate 
from a solution. This is the reason threads are hung in syrup, 
out of which it is desired to have the candied sugar crystallize. 
In like manner you may notice that in calcareous regions the 
radicals of plants which trail in water, are laden with the sub- 
stances held in solution. Well, the algae thus developed within 
solutions intended for injections, produce like effects. You 
therefore see how objectionable it is to allow the development 
of this vegetation. 

Any of the antizymotics will prevent this development. 
You know there are a great many antizymotics, and they act in 
very different ways. We must select those which possess the 
greatest efficacy and are the least harmful. Mercurial salts are 
numbered among antizymotics, but you well know why you will 
not make use of them. You will select something harmless, like 
borax, to which Mr. Dumas called attention, recommending it as 
an excellent antizymotic. I explain its effects by saying that it 

M 



178 PRINCIPLES AND METHODS OF THERAPEUTICS. 

acts the part of an alkaline body, while these low forms of vege- 
tation require an acid condition for their active development. 
Dutrochet had already established this, and I have applied that 
theory to the development of thrush. You may also use hydro- 
late of eucalyptus, glycerine or bay-cherry water. Of late years, 
Mr. Lumonsin has advised the use of salicylic acid, whose chief 
property is its being an antizymotic; that is, capable of de- 
laying very materially the development of all low organic forms. 
This acid may give good results, but phenic acid, even in the 
proportion of a one-thousandth, is better, because it is, beyond 
all comparison, more active. A solution of benzoic acid might 
be used, as has been done by Messrs. Gosselin and Albert Robin. 
Vanillin would also give good results. By the use of any of 
these agents you might delay the development of algae long 
enough for you to use up the contents of a phial before they 
could make any considerable headway. 

We now come to the precautions which are to be observed 
with regard to the individual upon whom the injection is to be 
made. When you have to administer an injection you must be- 
gin by estimating the depth to which you will have to penetrate, 
because the injection is not to be applied in the cells, and deep- 
seated areolae of the dermis, and the adipose cellular tissue that 
fills it. You have to penetrate, not under the epidermis, as has 
been stated by a university professor — you can readily imagine 
that nothing can be introduced under the epidermis — neither 
within the dermis, as I have told you that this has serious ob- 
jections, and that such punctures are the cause of most disa- 
greeable accidents, particularly of eschars. You must not 
operate on the basement layers of the dermis, and in those areolae 
which contain more or less globular masses of adipose cellular 
tissue ; this would give rise to eschars, inflammations and deep- 
seated furuncles. You must penetrate into the subjacent lami- 
nated cellular tissue; you must reach the superficial, and even 
the deep-seated fascia superficialis. This is the reason why I am 
opposed to the use of the word hypodermics, introduced into 
science by Behier, because it more particularly applies to the 



HYPODERMIC INJECTIONS. 179 

adipose cellular tissue underlying the dermis. It is, therefore, 
important you should know how deep you have to penetrate. 
If the patient is spare of flesh, it is evident the distance must be 
short ; but if the person is obese, you will have to introduce the 
whole needle. You must, therefore, in the first place, make a 
fold in the skin, so as to ascertain its thickness. You must also 
make sure that you are not in proximity to any considerable ves- 
sel, for it would be unadvisable to open it. If it is a vein, a 
small quantity of blood might flow out, which would be enough 
to alarm many persons ; besides, you might introduce some of 
the substance into the vein. Now, I must tell you that there 
are persons who have been, as it were, struck by lightning by a 
hypodermic injection, some of the substance of which had been 
introduced into a vein. This has happened with morphine, 
among persons who were in the habit of taking it. They 
always recover, because organic poisons hardly ever kill, unless 
they prove fatal on the instant. However, it is always un- 
pleasant to see one's patient collapse. This has not only hap- 
pened to patients, but also to physicians who practiced injections 
upon themselves. Dr. Chouppe, in a self-administered injection 
of morphine, having been so unfortunate as to meet with a vein, 
was overtaken by syncope. For, although absorption takes 
place rapidly outside of the vessels, it is not, however, so instan- 
taneous as in the present case. 

Now that you know the precautions which are to be taken 
with regard to the instrument, the solutions and the subject, let 
us examine the manner of operating. 

How will you proceed? You must carefully learn this, be- 
cause many physicians are ignorant how an injection should be 
given. You make a fold in the skin, taking it up in all its 
thickness, and it is at the base of this fold, in a parallel line 
with its direction, that you introduce the needle. You then 
slowly press upon the piston without letting go the fold you 
hold with your left hand, and you thus introduce the solution. 
You will proceed slowly, especially if the quantity of liquid to 
be injected is rather considerable. The degree of slowness must 



180 PRINCIPLES AND METHODS OF THERAPEUTICS. 

be greater and more deliberate in proportion as the cellular tissue 
is less lax and less lamellated. If the tissue shows some adher- 
ence if the skin is not readily detached, you must proceed with 
still greater slowness, because, if you inject with any degree of 
force either you over distend the lamellae of the connective tis- 
sue, or else you may even happen to tear some of them. You 
then have rather serious consequences : a plastic exudation and 
an inflammatory development, which are an obstacle to absorp- 
tion. In short, without obtaining good results, you meet with 
disadvantages. It is, therefore, a matter of necessity to impel 
the injection with great caution. 

I have now a remark to make ; if you have to deal with a 
person of dark complexion, young, thin, belonging to southern 
or Semitic races, or simply of Spanish race, you must be on your 
guard, because you will meet with a stubborn resistance. You 
must know this, so that you may have the courage to force your 
way through. On the contrary, when you have to deal with a 
person of light complexion, having a fresh and rosy skin, like 
an English woman, the needle then penetrates without difficulty. 
Penetration is the easier in proportion to the fatness of the sub- 
ject. This reminds you of what you may notice when endeav- 
oring to break the stem of a plant overflowing with sap : it 
breaks, when in that condition, very readily ; but if it is par- 
tially dry, it bends and does not break. Just so when the skin 
is very much distended, the needle penetrates without any 
trouble. 

What you observe there in the physiological state, you again 
find in the pathological state. I still have in my hospital service, 
a patient suffering from a singular nervous affection of the right 
side of the face and the right arm, accompanied by atrophy of 
the muscles and hypertrophy of the loose connective tissue. 
Well, in this distended skin, swollen as it seems with juices, the 
needle penetrates as by its own weight. 

With regard to the local effects, there is at first a stinging, 
pricking, burning sensation, which occasionally is but little 
noticeable, but often very painful. Thus injections of aconitine 



HYPODERMIC INJECTIONS. 181 

cannot become of general use, because of the hot and burning 
sensation they produce ; these are so intense that patients prefer 
keeping their neuralgias rather than submit to an injection. 

After a given time the pain subsides, and you observe a small 
inflammatory areola forming itself around the puncture, and both 
the skin and the whole course followed by the needle become 
swollen. In a certain number of cases a real urticaria is even 
developed. At the same time, there is an exaggeration of sensi- 
bility, and if you question persons who know how to observe 
their own sensation, they will tell you that the mere passing of 
the finger over the puncture is unpleasant to them. But hardly 
have two, three or four minutes elapsed, than all these 
phenomena are reversed, that is, hypersesthesia is replaced by a 
deep sedation, by marked reduction of sensibility to pain, and 
even, in a certain number of cases, by a real absence of pain. 
This phenomenon is general. It has been noticed by conscien- 
tious observers, who only make use of a single remedy. Thus, 
for example, Pr. Norniand, 1 to whom we are indebted for a 
knowledge of the parasite which is considered as the cause of 
the Cochin- Chinese diarrhoea, has communicated to me his obser- 
vation upon the. absence of pain caused by hydro-bromate of 
quinine. It is present, whatever may be the substance used, and 
what is singular, the same phenomena are observed even when 
only distilled water has been introduced. 

1 Normand. Memoirs upon Cochin-Chinese Diarrhoea (Archives of Naval 
Medicine, 1877, Vol. XXVII.) 



182 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XVI. 
Hypodermic Injections— [ Continued.] 

Common Local Phenomena — Local phenomena which vary with the substances 

injected. 
Diffused General Phenomena — Injections of water. — Phenomena of imbibition, 

of sympathy of contiguity, and of continuity. 
Rapidity of Action of Hypodermic Injections — Their constancy of action. 



Gentlemen: 

We must resume the consideration of the local phenomena, 
but especially of the secondary phenomena. Whatever may be 
the nature of the substance used, these phenomena of analgesia 
are constant. Analgesia is easily recognized ; when, at the 
expiration of a short time after the introduction of a liquid, you 
examine, with the aid of a pin, the sensibility of a region, you 
find that, after having evinced a greater sensibility to puncture, 
(immediately after the injection,) that same region has grown less 
sensitive. And this insensibility, at times, even extends very 
far. In order to form a correct idea of this reduction of sensi- 
bility to puncture, you must be on your guard against certain 
causes of error. Comparatively little is known as to the 
normal distribution of sensibility on the surface of the body. It 
is not everywhere equal ; and if you happen to puncture in the 
pit of the stomach, you will notice a greater degree of sensibility 
than in the neighboring regions. The result of this is, that, 
having made an injection in the upper portion of the right 
abdominal muscle, if you puncture in the pit of the stomach, 
you will be led into error by comparing two regions in which 
sensibility is not the same. Comparison should be established 
between analogous regions, or, what is still better, with the 



HYPODERMIC INJECTIONS. 183 

homologous region on the opposite side. These are trifling 
details which, from a practical point of view, have great im- 
portance. But the general fact is, that analgesia appears after a 
few minutes, and, in a number of cases, extends to anaesthesia, 
properly so called. You can measure this ansesthesis with the 
aid of a pair of compasses; you will find that a diversion of 12 
or 15 millimetres gives rise to a single sensation, while on the 
homologous region you will obtain a dual sensation. Conse- 
quently, you see that it is real ansesthesis which is manifested. 
In making this experiment, care must be taken to place the two 
branches of the compasses upon a transverse line with regard to 
the nervous fibres of the region. For here, again, there are 
illusions of quite another character which recur in observations 
upon ansesthesis ; if the arms of the compass are placed in the 
direction of the nervous branches, the sensations will be super- 
posed, and however great the distance, but one sensation is 
realized ; if, on the contrary, the compasses are less opened, but 
are placed crosswise with regard to the nervous fibres, you 
w T ill experience two sensations. 

These results are obtained upon subjects in good health. 

You see how difficult it is to measure sensibility, unless these 
points are known in advance. Well, a great number of authors 
who have spoken of sensibility and given its bounds, have be- 
stowed no attention upon these anatomical and physiological 
peculiarities. We even have hypothermesthesia — this is a word 
I have had occasion to coin for the purpose of expressing the 
least sensation to cold — for if you make an injection of aconitine, 
you will observe that even with a bright redness of the region, 
there is much less sensitiveness to cold than on the adjoining 
region, although this may be pale. 

You see that most of the modes of peripheral cutaneous sensi- 
bility can be reduced or extinguished. Well, while this reduc- 
tion exists, it may sometimes happen that you will observe a 
painful hyperesthesia; that is to say, there will be either spon- 
taneous or provoked pain. Thus again, after having made an 
injection of aconitine, even when the region is in an analgesic, 



184 PRINCIPLES AND METHODS OF THERAPEUTICS. 

anesthetic condition, it may happen, in a number of cases, that 
you will provoke a very sharp pain by passing the finger over 
the skin. This pain irradiates along the nervous tracts of the 
region. 

These facts, as you will observe, are extremely remarkable. 

When these general phenomena common to all injections have 
passed away, they are followed by those which are peculiar to 
the substance used, and which come and conceal the former. 
According to the nature of the substance introduced, you will 
have particular phenomena, which will greatly differ. Morphine, 
and in general, the alkaloids from opium, also ether or chloro- 
form, will give rise to phenomena of stupor, of narcosis, which, 
according to cases, will cause a reduction of sensibility or a cessa- 
tion of pain • finally, if they are hypnotics, you will observe that 
sleep will follow. 

Conine always induces phenomena of sedation of the motor 
system, and these are evidenced either by a reduction of motility, 
or by a cessation of spasms or convulsions. 

Aconitine and veratrine also cause a cessation of pain. Aco- 
nitine overcomes all neuralgias of the fifth pair. There is 
reason to doubt whether it acts in the same way as morphine, 
hence I place it separately. Quinine and its congeners will 
determine all the phenomena of sedation which tonics produce. 
Judging from my own experiments, picrotoxine will act in the 
same way; so also will strychnine, which exerts its influence 
upon the marrow. Ergotine brings on an excitation of the 
smooth fibres. With mercurial salts, or iodide of potassium, re- 
sultant antiplastic effects will be obtained. 

We now come to an interesting question which is not yet 
satisfactorily settled in the minds of a number of physicians. 
Are the particular effects of medicaments generally distributed 
throughout the whole system, or is there a greater intensity of 
effect in the region in which the injection has been made? In 
other words, do substances only act after having been absorbed, 
or is there, on the contrary, a topical action first excited by them, 



HYPODEEMIC INJECTIONS. 185 

and then a development of the general phenomena which they 
entail ? 

The question still remains open, but the prevailing opinion, 
and that which I adopted when I first made my experiments, 
is that medicaments introduced by injections exhibit a predomi- 
nance of particular effects in the region itself in which they have 
been introduced. A number of able men assert the contrary. 

Great practical importance attaches to the settlement of this 
question. If it is believed that substances deposited under the 
skin must first be absorbed, and then return to act upon the 
region in which they have been placed, the injection might be 
made anywhere. This is the conclusion arrived at by those 
physicians who believe that action is diffused. On the contrary, 
many, with myself, believe that while there is considerable 
action in the balance of the organism, the greatest energy is ex- 
erted in the region in which the deposit has been made, and in 
its vicinity. When we desire to act. upon a nerve affected with 
neuralgia, or upon any organ which requires being modified, we 
are prompted to operate in the neighborhood of and as near as 
possible to the organ. Hence it becomes indispensable to prove 
to you that there is a particular and direct action exerted over 
the region. 

The topical actions exerted by hypodermic injections may be 
divided into two groups. In the first place, those exerted in the 
very region in which the deposit is made. It seems impossible 
not to believe that an active substance should determine there 
more intense local effects than in the rest of the organism. But 
this is not all. When you deposit a gramme of an active solu- 
tion within a small space, you can see the effects of this solution 
spreading afar. And the proof of this diffusion, of this propa- 
gation, may be deduced from a number of circumstances which I 
shall now review. 

In the first place, there is a marked rapidity of effect upon 
neuralgias : for example, when the aetive substance — let us say 
morphine — is introduced in close proximity to the aflected nerve. 
In the case of a sciatica of long standing, if you have already 



186 PRINCIPLES AND METHODS OF THERAPEUTICS. 

given morphia internally, you will have observed that sedation 
takes place, let me say, in about an hour ; but after introduction 
under the skin, it shows itself within a few minutes. But, bet- 
ter still, you have only to make this other experiment : In a 
case of sciatica you inject into the arm 1 or 2 centigrammes of 
morphine; the following day, the crisis being due at the same 
hour, you make the same injection, but in proximity to the seat 
of the sciatic nerve ; you will then observe that while the day 
before it took some time to ease the pain, on the present day the 
delay is much shorter. The delays should be of equal duration, 
if sedation was due to the substance having been absorbed and 
carried into the circulation; but such is not the case. 

Cases of double sciatica are rare, but when you happen to meet ' 
one you can make the following experiment : Inject one day, in 
the left thigh, the substance which is to narcotize the sciatic 
nerves, and you will observe that the left nerve is by far the 
most influenced ; on the contrary, the right one suffers for a longer 
time, and does not receive the same ease as the other side. The 
following day do the contrary, and you will have the reverse of 
the day before. This is very remarkable and demonstrative; 
consequently, it is impossible not to recognize that there is in 
this case a direct influence exercised on the region by the sub- 
stance introduced under the skin. 

Some time ago, a careful analysis was made of the modifica- 
tions of sensibility resulting from the introduction of narcotic 
substances under the skin, and it was observed that in a consid- 
erable region the tactile circle is gradually increased in propor- 
tion as the substance penetrates. Thus, immediately after intro- 
ducing the substance, the region is still quite sensitive, but after 
some time has elapsed, it becomes necessary to open the branches 
of the compass in order to obtain sensations. 

No substance is better adapted to the analysis of these 
phenomena than aconitine. When yon introduce half a milli- 
gramme of aconitine under the skin, you observe phenomena of 
aconitism — that is, all those which aconitine is able to determine ; 
but they are observable in the injected region at an earlier date, and 



HYPODERMIC INJECTIONS. 187 

with greater intensity than in the more distant regions, and it is 
evident that yoa have really determined there deeper therapeutical 
modifications. As you know, aconitine causes a sensation of prick- 
ing — something that resembles an itching. When it is introduced 
under the skin it determines a burning sensation, which, besides, 
will also manifest itself about the mucous surfaces. But these 
pricking and burning sensations first exist in the region in which the 
puncture has been made ; they then gain more and more extended 
regions, spreading themselves according to a course which exactly 
corresponds with that of the nervous divisions in the region. 
If, for example, the puncture is made on the leg, the sensations 
will spread along the course of the fibula, so much so, that those 
persons who frequent our hospitals, guided by the course of the 
pain, are able to give an exact description of the anatomical sub- 
division of the femoro-popliteal regions. They will tell you 
that the sensation which first existed in the region of the injec- 
tion, gradually descends. Finally, when diffusion has taken 
place almost throughout the whole limb, you will again notice this 
peculiarity : if you happen to rub over a region somewhat dis- 
tant from the seat of the injection, and one in which modifica- 
tions can only have been produced through diffusion, you will 
determine a sort of shooting pain through the nervous branches 
in connection with those of the region which has been rubbed 
over. With a dose of only one milligramme, this phenomenon 
does not present itself in the remainder of the organism. This is 
a positive proof, added to those already given, that the action of 
an injected substance is diffused and propagated in diminishing 
strength as we progress from the seat of the injection. 

We must now account for the way in which this propagation 
takes place, and also explain how it is that a substance intro- 
duced under the skin produces a greater effect in the region 
where it has been placed, than in the other regions of the 
economy. 

In watching what follows a hypodermic injection you will 
notice that the ridge formed by the solution subsides somewhat 
rapidly. This is due to two reasons : in the first place, absorp- 



188 PRINCIPLES AND METHODS OF THERAPEUTICS. 

tion sets in very early, and then a capillary diffusion takes place 
in the areolse of the cellular tissue, which is the more rapid in 
proportion as these areolae are wider. Added to this there is a 
shrinking of the skin and contractile tissues. The result of this 
is, that the substance which at first only occupied a small space, 
now covers a wider range, and spreads itself, not only in the 
subcutaneous cellular tissue, but also through the vascular 
orifices and along the nervous routes. 

There is yet another mode by which these actions are propa- 
gated; it is that which, ever since John Hunter, has been desig- 
nated by the name of sympathy of continuity and contiguity ; 
what I explain by the " polarization of the histological ele- 
ments." The fact is readily illustrated, as far as the muscular 
system is concerned. In certain morbid cases I have shown that 
by striking with the tip of the finger upon a muscle, first a knot, 
then waves are produced, which extend to the extremity of the 
muscular fibres; the spreading of these waves in this way can 
only be produced by a propagation of the excitation caused by 
percussion at a given point. There are no nervous fibres that 
can account for it. 

Finally, transmission takes place by reflex actions, or by others 
which greatly resemble them. You know that when we excite 
a certain region, we give rise to excitations in a region in ner- 
vous connection with it. I shall mention but a simple example : 
it is that of the great sympathetic nerve which conveys peripheric 
excitations into the depths of the parenchymatous organs ; thus 
phenomena of sedation are transmitted in this way from the 
part that has been calmed, to parts in nervous connection with it. 

I called attention some time ago to phenomena of which I 
have already spoken here, and which I called echoes. That is 
something analogous to reflex actions. 

These echoes consist in this : when, for example, there is a 
pain in the thigh, it is reverberated in the upper portion of the 
trunk ; if a pain is seated at the base of the thorax, it may 
reverberate as far as the little finger; in short, the pain 
follows the known course of the cutaneous nerve of the arm. 



HYPODERMIC INJECTIONS. 189 

We do not at present know why these reverberations occur ; but 
you understand, that since they take place with reference to 
pain, they may also exist with regard to sedation, which would 
thus be propagated by the agency of echoes. Upon the whole, 
the important modification, from a physiological and therapeuti- 
cal point of view, which is determined in a more particular 
manner than anywhere else, either at the place within which the 
medicament has been deposited, or within a more or less extended 
region, may be explained by the three conditions I have just 
mentioned: first by imbibition, then by sympathy of continuity 
and contiguity, and finally by those phenomena of echo, which 
are analogous to reflex phenomena, and to which I have just 
called your attention. 

Among these conditions, imbibition is one, by the aid of which 
we can explain the strange phenomenon of analgesia, which fol- 
lows after all subcutaneous injections, no matter what may be the 
substance introduced under the skin. It is really wonderful to 
think that you may introduce under the skin a substance like 
strychnine, which excites, or aconitine, which burns, or morphine, 
which narcotizes, or even pure water, or distilled water, and that 
in every case, after a given time, analgesia will surely follow, as 
an invariable result. 

To my mind, the governing condition in all these cases seems 
to be that, whenever a substance is introduced under the skin, 
whatever may be its nature, water is invariably introduced along 
with it, and that it is the presence of this water in more or less 
considerable quantities, which at first predominates. This water 
penetrates as well into the interstices of the connective tissue as 
into the histological elements, for it is well you should know that 
these are always more or less laden with water, or, in other 
words, they are hydrated. They are always very much so 
among plethoric persons, and with those in whom anaemia has 
induced dropsies. In other cases they are very dry and thin. 

If you compare the histological elements of a healthy region 
with those of an analogous but inflamed region, you will find 
that these are more voluminous than the first. This has often 



190 PRINCIPLES AND METHODS OF THERAPEUTICS. 

been described ; the elements of the cutaneous tissue are greatly 
swollen when the inflammatory process is considerable, and they 
then become turbid and granulous. There are, therefore, differ- 
ent degrees of hydration, and it is this hydration which causes a 
reduction in the several modes of sensibility, and particularly a 
reduction of sensibility to puncture and to pain. 

We may borrow from pathology a point for comparison, by 
observing what takes place in anasarcous subjects. Wherever 
anasarca is present, the skin is almost insensible, and sensibility 
to pain is reduced. But if you explore exactly above the point 
at which anasarca ceases, you will find that sensibility is unim- 
paired. The cause of this phenomenon is not due to a general 
but to a local condition, resulting from an infiltration not only 
of the cellular tissue, but of the histological elements them- 
selves. 

This is the reason why such marked effects of sedation from 
pain are obtained by simply injecting a syringeful of pure water 
under the skin. 

This fact was first observed in the hospital service of my 
excellent friend, Dr. Potain, by Mr. Dieulafoy. By a mistake, 
pure water was injected, and yet the patient affirmed that his 
pain had been soothed. This is not the idle fancy of an invalid. 
I have observed numerous cases in which sedation was obtained, 
but not of so long duration as when sedative substances were 
used. I had a patient suffering from one of those neuralgias 
which I call congestive — this is one of the cases in which aqueous 
injections are most successful — who was in the habit of receiving 
morphine injections. Wishing to avoid his becoming accus- 
tomed to these, I gave him an injection of pure water, but left 
him under the belief it was morphine. The following day he 
complained that the pain had re-appeared after a time, and that 
probably the solution had lost its strength. On that day I made 
him a real injection of morphine, and he was relieved from pain 
during a long time. Whenever I repeated the water injections 
he complained of only having had temporary sedation. I have 
often noted these facts which have been remarked by a great 



HYPODERMIC INJECTIONS. • 191 

many observers since Messrs. Potain and Dieulafoy. And 
recently a work has been published on this subject by Dr. Mon- 
tecorvo, of Rio de Janeiro. 

Sedation lasts as long as hydration does, and when the water 
has disappeared the pain returns as before. These are therefore 
only temporary effects. 

I have now to speak of diffused or generalized effects. Of 
course these are similar to those you observe upon the introduc- 
tion of the same substance by other ways ; they only differ from 
those by the greater rapidity with which they show themselves, 
by their constancy, and the greater intensity which they present. 
I shall now review these different peculiarities, and it is import- 
ant you should fix them in your minds, because they in a great 
measure constitute the superiority of the hypodermic method. 

In certain cases rapidity is wonderful. It is long since Eulen- 
burg's experiments have proven this. It is only inferior to that 
of medicaments introduced directly into the venous system. 

Here is one of these experiments which was made upon a 
rabbit whose jugular vein was opened,, so as the more readily to 
gather some of its blood. Some amygdaline was injected under 
the skin of its thigh, and after three minutes, a few drops of 
blood having been collected, emulsine was added to it, develop- 
ing a faint odor of bitter almonds. After a lapse of five min- 
utes this odor became very strong. Consequently, in this case, 
it only required from three to five minutes for a considerable 
proportion of the active principle to pass into the blood. The 
experiment was likewise made with yellow prussiate of potash, 
and it was noticed that while it took fourteen minutes for this 
substance to first show itself in the urine, when introduced by 
way of the stomach, it only required five or six when introduced 
under the skin. 

These observations prove that absorption, circulation and 
elimination have taken place within a delay of three, four or five 
minutes, since at the expiration of that time the urine shows the 
presence of a considerable quantity of active principle. Pilo- 
carpine acts even more promptly than those substances. It is an 



192 PRINCIPLES AND METHODS OF THERAPEUTICS. 

active principle derived frbm pilocarpus pennatifolius, (rutacese,) 
or jaborandi, according to Dr. Continho. I very often use this 
alkaloid, in doses of 2 centigrammes, to bring on salivation and 
sedation in the beginning of an influenza, or during the progress 
of cardiac affections. At times, pilocarpine shows its effects in 
an incredibly short period. It has once or twice happened to 
me that a minute and a half after giving the injection, the face 
is seen to redden, as if the two sympathetic nerves had been 
severed. Half a minute later all the phenomena of redness, 
heat and sweat are in full development ; that is to say, that two 
minutes after the injection the sweat is flowing, and salivation is 
abundant. I do not say this is invariably the case, because it 
usually requires five minutes, but I have witnessed the above 
facts. 

This medicament acts with an almost incredible rapidity, which 
about equals that of medicamental substances introduced by way 
of the respiratory organs. This rapidity will appear still more 
surprising when you reflect upon the time required for a full 
circulation — that is, for a globule to travel through the whole 
circulatory circle. At first thought, you might suppose that 
since there are about sixty cardiac propulsions in a minute, the 
blood must travel in a sixtieth of a minute from the heart to 
the wrist. But you must remember that the blood globules 
you feel at the radial are not those which were in the heart at 
the instant of the systole. Each pulsation of the heart puts in 
motion the blood-stream which is before it. It is a propagation 
from proximate to proximate, and not a translation of blood 
from the heart to the periphery. 

Hering's experiments have proven that it requires not less 
than a minute for a blood globule to perform its circuit. Con- 
sequently, for pilocarpine to have acted within two minutes, ab- 
sorption must have taken place with the greatest rapidity, since 
that length of time was sufficient for it to circulate and be elimi- 
nated by the salivary and sudoriparous glands. 

In a vast number of cases that is what forms the great superi- 
ority of the hypodermic method, because we often have to act not 



HYPODERMIC INJECTIONS. 193 

only promptly, but we must also introduce into the circulation 
a considerable quantity of active substance; hence, by this 
rapidity of introduction you are enabled to act promptly and to 
introduce a large quantity of active principle. 

Another peculiarity deserving of notice is the constancy of 
effects. CI. Bernard, 1 by introducing every day 3 milligrammes 
of curara in the same rabbit, and continuing this experiment for 
several weeks, invariably obtained the same phenomena within 
the same time and with the same intensity. After twenty min- 
utes, symptoms of mild curarism would appear, and always last 
about forty-five minutes. On the other hand, it has been observed 
that when the same active substance is continuously introduced 
by any other way, this constancy of results is never obtained. 
This is due to the fact that in the stomach destructions take 
place, and absorption is either slow or rapid, and exercised upon 
the whole or only a fraction of the active substance. There is 
besides, a question of power and intensity of action which has 
been observed ever since the method was first brought into use. 
Those who have studied the effects of quinine have noticed that 
when introduced under the skin in small quantities, if it chanced 
not to produce an inflammatory condition, causing an obstacle to 
absorption, it determined the same physiological and therapeu- 
tical effects as quantities four or five times greater given through 
the stomach. 

The difference with atropine is even greater. A centigramme 
is a toxical dose, but I have had a subject to whom I have given 
as much as 4 and even 10 milligrammes within the twenty-four 
hours, which are enormous doses, and yet produced no effects. I 
began to think he resembled herbivorous animals j but an injec- 
tion of a milligramme under the skin determined all the phe- 
nomena of atropism. 

What I observe with regard to atropine, I might repeat as to 
all medicaments which have been given by the stomach and 
hypodermically. The advantage is always in favor of the latter 
method. 

1 CI. Bernard. " Lessons upon the Effects of Toxical and Medicamental 
Substances." Paris, 1857. 



194 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XVII. 
Hypodermic Method — [ Continued. ] 

Different effects of various substances administered through the stomach and 

by the hypodermic method. — Causes of this difference. 
Local accidents attending hypodermic injections. — General accidents. 



Gentlemen : 

It has been estimated that the quantity of sulphate of quinine 
necessary in an injection is only one-sixth of that required when 
given by the stomach. All the experiments I have made with 
hydrobromate of quinine, all those which have been repeated 
after me by Dr. Normand, confirm this superiority. I have no 
hesitation in affirming that 40 centigrammes of quinine under 
the skin — I can now say as much for cinchonidine — give the 
same results as 1.50 grammes by way of the stomach. Hence, 
by injecting morning and evening 20 centigrammes of hydro- 
bromate of quinine, paroxysms of fever are averted exactly as if 
1.50 gr. or 2 grammes of sulphate of quinine had been taken. 

This is a great result, and as it can be obtained without any 
possible danger to the cellular tissue, there is every reason to 
make use of it, and adopt it as a method of treatment. 

As I stated before, atropine shows even greater differences in 
doses between the two methods. It may be said that, in general, 
3 or 4 milligrammes, by way of the stomach, give the same 
results as 1 by the hypodermic method. This is in about the 
same ratio as with sulphate of quinine. With morphine the 
difference is less, and an injection of 1 centigramme by the hypo- 
dermic syringe does not give any more marked phenomena of 
narcosis than an equivalent quantity of syrup of morphine or 
laudanum given through the stomach. 

But there are cases in which this difference is much greater, or 



HYPODERMIC INJECTIONS. 195 

rather, there are subjects with whom morphine hardly shows any 
effects by way of the stomach, while it is quite efficient when 
injected. Consequently constancy is one of the fundamental 
characteristics of the hypodermic method. 

There are other substances which it is important to compare 
according as they are used by either of the two methods of intro- 
duction. 

Aconitine does not offer any very great differences as to 
intensity of effect, whether introduced under the skin or given 
through the digestive organs. But this is providing the stomach 
is perfectly healthy, and is ready for rapid absorption, all of 
which conditions are rarely met with. Otherwise, if the stomach 
is in a saburral condition, if it still contains alimentary residuums 
and all the ferments accompanying them, when aconitine is 
introduced, it will produce no effects. I have seen persons who 
have taken milligrammes of the best aconitine, and who have 
hardly felt any of its effects, because it is an unstable substance, 
which is easily destroyed by any of the chemical bodies, aud 
especially by ferments. But in a healthy stomach the difference 
is not very great; it is as one to two. That is to say, if 1 mil- 
ligramme of aconitine is required, when given internally, to pro- 
duce marked physiological effects corresponding with the thera- 
peutic wants, only half of that quantity is necessary when intro- 
duced under the skin. This difference is not without its value, 
but it is not as great as in the case of quinine. 

On the other hand, ergotine, when it is introduced by the 
hypodermic method, would seem to offer the other extreme. 
The substance here mentioned is not the alkaloid from ergot ; 
that is not as yet to a certainty known ; but it is a more or less 
concentrated extract which represents the principles and action 
of ergot, not intensified, but rather reduced. We have Bon- 
jean's ergotine, which is an alcoholic extract of ergot ; we also 
have a more concentrated extract, lately prepared by Mr. Yvon. 
Yvon's extract, which is a light topaz-tinted liquor, is so con- 
centrated, that one gramme is equivalent to one gramme of ergot, 
while Mr. Bonjean's somewhat dense extract is much inferior to 



196 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ergot itself. My own experiments have satisfied me, that to pro- 
duce the same therapeutic effects, it is necessary to use no less 
than five times as much of it as of ergot. 

But this solution of ergotine has the advantage that it can be 
made into a lotion and injected under the skin. Recent experi- 
ments seem to indicate wonderful differences between the hypo- 
dermic and stomachic effects of this substance. It would appear 
that by introducing 10 or 15 centigrammes of Bonjean's ergotine, 
a hemorrhage is stopped the same as by giving gramme 1.50 of 
powdered ergot. 

I have reason to think these are exaggerations. For my part, 
I have never seen any effects from ergotine injections indicating 
such intensity of action. I have observed effects, but I never 
injected less than 25 centigrammes at a time. In certain cases I 
have seen an hemorrhage stopped ; but if we are to believe the 
recent observations commnnicated to the Therapeutic Society a 
few months ago, a difference of forty-fold separates the action of 
these injections from that of ergot itself. In fact, it is claimed 
that an injection of 10 or 15 centigrammes of ergotine produces 
as much effect as 4 grammes of ergot. I cannot admit this. I 
very much fear, that by mistake a causal relation has been 
thought to exist between the introduction of the substance and 
the discontinuance of the hemorrhage, while, in reality, there 
was nothing more than coincidence and spontaneous cessation. 

However this may be, it is indispensable you should under- 
stand why these differences are possible, and why such great 
divergences can exist' in the intensity of action of certain sub- 
stances when introduced under the skin, or given through the 
stomach. 

In the first place, it is important to know whether the sub- 
stance is destructible or not in the prima? vise. It is evident, that 
if a resisting substance is introduced into the stomach, it will 
finally be absorbed. Absorption will take place more slowly 
through the skin, but still it will take place, and a time will 
come when, having reached the parenchyma in a sufficient quan- 



HYPODERMIC INJECTIONS. 197 

tity, it will determine all the effects of which it is capable. In 
this case there is no difference between the two methods. 

There is another circumstance, which is the greater or less 
degree of adhesiveness of the substance introduced to the areolae 
of the cellular tissue and to the organs in the midst of which it 
spreads. This adhesiveness is real. 

In the case of aconitine, I have called your attention to the 
great intensity and endurance of its local effects. Not only does 
it cause a sharp, burning sensation and shooting pains, but those 
effects continue, at times, for two hours. I have seen subjects 
continue a whole afternoon in the agony caused by aconitine in- 
troduced under the skin. This proves its local adhesion, and 
this adhesion must have its importance, because as the substance 
is not carried away like some others by the circulation, its effects 
are not distributed through the whole system. 

There is a third reason for the difference in the intensity 
of effects between substances introduced under the skin and those 
given through the digestive organs. These effects may depend 
on the system over which their action is exerted. If the medi- 
caments or poisons exercise their action directly through the 
blood, and on the blood itself, it is evident that if they penetrate 
in large quantities at a time, that action will be violent, fulmi- 
nant, instantaneous. On the contrary, if substances exert their 
influence on the nervous centres, and if this influence is only 
exerted by the penetration of those substances into the elements 
of the nervous system through a sort of temporary combination 
with these elements, a considerable time is required for this to 
take place, and although you may introduce into the circulation a 
large quantity of active substance capable of producing effects on 
the nervous system, these effects always requiring a certain time 
in order to be produced, there will be no great advantage in in- 
troducing substances hypodermically rather than through the 
stomach, because if they are not destroyed they will be absorbed 
with sufficient rapidity to penetrate into the circulation and 
thence into the parenchyma. 

Now those combinations between the substances and (lie 



198 PRINCIPLES AND METHODS OF THERAPEUTICS. 

elements exist. A certain number of perceptible modifications 
have already been observed in the histological elements of the 
nervous system, when these have been impregnated with an 
enormous quantity of toxical principles. These experiments 
have not as yet been fully carried out, although the first of them 
dates back some ten or twelve years. 

They open up a new path and enable us to understand what 
was already indicated by inductive considerations, that substances 
probably penetrate into the histological elements. 

I shall give you a few examples. Let us suppose that you 
rapidly introduce into the blood phosphorus, oxide of carbon, 
nitrite of amyl, anaesthetics — in fact, any of those substances which 
act directly on the blood. They will act, producing what we 
might term lightning strokes. If you happen to introduce them 
by the subcutaneous method, and they come into the circulation 
in large masses, they will produce effects nearly as violent as by 
inhalation. And there will here be the widest difference between 
the effects produced hypodermically or by way of the stomach. 
If, on the contrary, you introduce substances which, like mor- 
phine, act on the nervous centres, there will be less marked dif- 
ferences, because these substances have to penetrate into the histo- 
logical elements, and for that purpose they require a certain time. 

I must now point out to you a few applications of these prin- 
ciples. I stated that we could in that way understand why cer- 
tain substances act almost as well through the digestive organs 
as by injection, and how with others the contrary is the case. 

Take, for example, morphine. This is very stable, and also it 
requires considerable time to penetrate into the histological 
elements of the nervous system. These two conditions favor its 
introduction through the stomach. 

Quinine has not the same qualities. It is destroyed ; in the 
literal sense of the word, destruere — to lose structure. It readily 
changes into quinidine and quinicine; the former is almost with- 
out effect ; the latter has none at all. Therefore, quinine, when 
in the stomach, without disappearing, (you might take up the 
contents of the stomachic retort and still find the alkaloid,) may 



HYPODERMIC INJECTIONS. 199 

become that residuum which is traced in the urine. For when 
a gramme of sulphate of quinine has been introduced into the 
circulation you recover in the urine 85 centigrammes of an 
alkaloid, isomeric with quinine; this is quinidine or quinicine. 
It is this species of destruction which prevents quinine from 
acting quite so well when given through the stomach as when 
introduced under the skin. It has to' penetrate into the elements 
of the nervous tissue^ but when introduced in the stomach it is 
less resistant than the alkaloids from opium ; hence there is a 
difference as between one and five, when the effects of the two 
methods of introduction are compared. 

Before passing judgment on the value of the hypodermic 
method, let me say a word on the local accidents attending in- 
jections. 

These may be divided into actual traumatic accidents and 
ulterior accidents due to the peculiar activity of the substances 
used. 

The first of all accidents, and that which most frequently 
happens, is a quick, sharp, agonizing pain produced in a more or 
less circumscribed region, and caused by the needle having come 
in contact with a nerve fibre. This is of no consequence, and 
the pain is not lasting. 

Another accident which, in certain cases, may assume more 
gravity, is when the needle penetrates into a vessel of some 
magnitude. Two secondary accidents may result from this. 
Either you cause a slight hemorrhage, which greatly alarms 
timid subjects, perhaps an internal hemorrhage — a kind of small 
thrombus which leaves an ecchymosis — or else in a number of 
cases there happens the serious accident I spoke of in the last 
lesson, and which strikes with a sort of sideration the subject in 
whose venous system the substance has been directly introduced. 
You may then witness an affecting scene : loss of consciousness, 
attended by deathly pallor, coma, and stertorous breathing. 
Something really fearful. However, it is very seldom that these 
accidents prove fatal, unless you happen to meet with a person 
affected with organic disease of the heart. 



200 PEINCIPLES AND METHODS OF THEKAPEUTICS. 

There is also another slight accident which may worry you 
if you do not know of it ; it is an emphysema localized around 
the puncture, and which at times assumes considerable import- 
ance. It has two origins, and may arise with all sorts of sub- 
stances ; it may be due to the fact that you are at fault in not 
having fully expelled all the air from the syringe, and that some 
of it has been introduced into the cellular tissue. This is of no 
consequence. But since hypodermic injections of chloroform 
have been made, a more persistent and larger emphysema has 
been noticed around the puncture. A crepitation is almost im- 
mediately observable, similar to that attending an emphysema 
due to anthrax, or to a pulmonary rupture. The cause of that 
emphysema is unknown, but I believe it may be due to a vola- 
tilization of the chloroform, which, although less volatile than 
ether, has still considerable vapor tension at 37°. Anyhow, 
these emphysemata appear unimportant. 

Let us now consider the ulterior accidents. In the first place, 
there is an exaggeration of all the physiological effects due to 
substances introduced under the skin ; these, as I just now 
stated, are capable of producing considerable effects in the 
locality in which they are injected. Hence, if you do not pro- 
portion the doses, you may determine toxical in place of thera- 
peutic effects. 

Finally, we have the effects due to the introduction of these 
same substances into a vein. These phenomena are unexpected ; 
the others may be foreseen, hence forestalled, by using moderate 
doses. When introduction into the vein takes place, you observe 
all the serious phenomena I have spoken of, and the case is em- 
barrassing. 

I shall tell you how to guard against these accidents. But I 
have first to mention certain initiative troubles resulting from 
excess of sensibility, and caused by the substances introduced 
under the skin. These are an exaggeration of the normal 
troubles. I told you the patient always experiences a slight 
flush of heat, a smarting pain, and usually exhibits a sort of 
erythema. When the phenomena are limited to this, and even 



HYPODERMIC INJECTIONS. 201 

to an eruption of urticaria, they have no great importance. 
But these irritative phenomena may assume more gravity. 
When the inflammation gives rise to an inflammatory node, it 
becomes a serious matter. This node seems due to two circum- 
stances ; in the first place, to the nature of the substance ; for ex- 
ample, it would seem, that picrotoxine produces larger exsudats 
than any other substance. In the case of a woman whom I 
attended for a labio-glosso-pharyngeal paralysis, and with whom 
I had obtained considerable success, since she grew worse each 
time I discontinued the injections, after some fifteen injections I 
noticed that her arms appeared like bags filled with filberts. I 
have had occasion to observe this in another case, but I do not 
hold it to be a general rule. 

The other circumstance is that these nodes are produced by 
the presence of irritating corpuscles in the substance inserted 
under the skin. In giving an injection, you must examine the 
solution very carefully, because the least particle of mineral or 
organic substance, or of an alga, which develops so easily, is 
usually sufficient to bring on a persistent sub-inflammatory de- 
velopment. And at times, after two or three weeks, you still 
find nodes under the skin. These are the two principal circum- 
stances in which these nodes are produced. But this is, as yet, 
of only minor importance. 

In certain cases, matters become more serious, and you will 
notice around the puncture not only an inflammatory node, but 
a more or less wide cedemato-phlegmonous puffiness, which 
alarms the patient, and should alarm you, because suppuration 
might set in. 

This is a real accident, important in itself, and besides, if you 
have to repeat the injections on the patient, a multiplicity of 
such abscesses would finally induce traumatic fever, and prevent 
you from continuing the treatment. These accidents are of fre- 
quent occurrence with certain substances, like mercurial salts, or 
sulphate of quinine, but we need no longer mention this latter, 
since the bromo-hydrate secures us against this danger. Besides 
this, there is a fifth degree, during which a gangrenous blotch 



202 PRINCIPLES AND METHODS OF THERAPEUTICS. 

is formed. I do not mean those blotches due to the introduc- 
tion of the substance into the dermis, but the sphacelus following 
the inflammatory development, and complicating it, by suppress- 
ing all sources of irrigation for the skin and subcutaneous cellu- 
lar tissue. This sphacelus has the double inconvenience of 
being very disagreeable at the time, and of leaving real cica- 
trices or indelible maculations. 

There is no necessary connection between the various affec- 
tions and the different accidents which may be determined by 
substances introduced under the skin. There are substances 
which cause violent pain and never any inflammation, while 
others awaken no sensitiveness, but produce nodes ; finally, 
there are some which occasion no pain, but give rise to suppu- 
ration. Picrotoxine, for example, is not felt, but always pro- 
duces a node. On the contrary, aconitine causes such agonizing 
pain, that patients, though relieved of their neuralgias, prefer 
not using the remedy ; but it never causes inflammations, unless 
some algse have been introduced under the skin. Therefore, 
pain and inflammation are not always present together. 

I have shown you the different results caused by the nature 
of the substance used ; the differences are equally great according 
to the subject receiving the injection. There are subjects with 
whom hemorrhages very readily take place ; it is those who have 
a hemorrhagic diathesis. But diathesis is not indispensable ; if 
there exist, in certain regions, conditions analogous to those of 
scurvy, the same hemorrhagic phenomena will be produced. For 
example, when injections are made in limbs which have been 
long stricken with immobility, and are affected with what Mr. 
Cloquet has designated under the name of local scurvy, the punc- 
tures will give rise to slight hemorrhages. What exists there 
under the influence of a traumatism, which has made immobility 
compulsory, likewise happens in spontaneous diseases. 

I have, at present, at the Hospital Beaujon, a patient who is 
affected with a trophoneurosis of the superior right half of the 
body. He has pains, and, at the same time, shows phenomena 
of muscular atrophy. But while the important organs, those 



HYPODERMIC INJECTIONS. 203 

which, like the muscles, have a peculiar structure, are being atro- 
phied, the cellular tissue, which is only an organ for filling up, 
is increasing in thickness. Hence, wherever the muscles have 
disappeared, this man shows a very thick subcutaneous adipose 
tissue. 

Well, I cannot get the needle to penetrate through this region 
without bringing on a hemorrhage. 

There are subjects who are also exposed to all the inflammatory 
accidents I have described, and to such serious lesions as gan- 
grenous phlegmons. This happens among those whose general 
sanitary conditions are bad, and among those who suffer from one 
of those diatheses, which cause important modifications in nutri- 
tion, or those who have reached the ultimate period in a chronic 
disease, with hectic fever. Thus, among tuberculous patients who 
have reached the last period among those under the effects, and 
of typhoid fever, in puerperal affections, in which suppuration 
so readily takes hold of any little traumatism, even that caused 
by an injection ; likewise in cases of albuminous and saccharine 
diabetes; in all those cases suppuration very readily sets in. The 
practical lesson to be drawn from these considerations is that 
medicaments should not be introduced by the hypodermic method 
in subjects who are in such precarious conditions, because the 
effects will not be satisfactory ; besides, you might easily appear 
to have harmed them, when your object was their relief. 

I turn back to general accidents, which, as I stated, consist in 
the penetration of active substances into the circulatory system. 
This is what must be done in order, as far as is possible, to pre- 
vent these accidents : you must, of course, carefully explore the 
region upon which you are about making an injection, so as to 
avoid all bluish lines : you will likewise avoid the large venous 
trunks, which anatomy has taught you to know. The needle 
must also be directed parallel to the general direction of the veins 
in the region ; in general, this direction is also that of the axis 
of the limb. You must also direct the needle from the centre 
towards the periphery ; that is, from the upper articulation of 
the limb towards its extremity. If the needle is thus guided, 



204 PEINCIPLES AND METHODS OF THEEAPEUTICS. 

should you be so unfortunate as to enter into a vein, absorption 
is never so rapid as when the injection is impelled in the direction 
of the blood current. To this might be added the precaution 
recommended by Behier : this consists in introducing the needle 
alone, when, if no blood appears, the injection is proceeded with. 
This process, however, does not afford implicit guarantees, be- 
cause it may give rise to false alarm should there be a show of 
blood, due to the conditions of the cellular tissue. It may also 
inspire unwarranted security, from the fact that if the needle is 
introduced along the course of a vein, there being no pressure 
exercised in a retrograde direction, there may be no renuence in 
the interior of the canula; and even if there should be^ the 
canula may be so small as to prevent an escape of blood. 



! 

i 






HYPODERMIC INJECTIONS. 205 



CHAPTER XVIII. 

Hypodermic Method [Concluded.] — Acupuncture. 
— Transfus ion. 

Substances for which the hypodermic method is unfitted. — Objections to the 
method ; its advantages preponderate. 

Acupuncture : Electro-puncture, parenchymatous, or substitutive method of 
injections. — Theory of, and criticism on, substitution. 

Introduction of medicaments through the vascular system. History of transfu- 
sion. — Principles. 



Gentlemen : 

Besides the objections attending hypodermic injections, we must 
admit this method does not always possess the superiority claimed 
for it over other ways of introduction. For example, there are 
subjects — tlie case is a rare one, but I must notice it — who are 
about as sensitive to a substance like atropine, when introduced 
in doses of one or two milligrammes into the digestive organs, 
as when introduced into the subcutaneous cellular tissue. 

There are other objections to this method : for example, nitrate 
of potash, cod-liver oil, and all other substances requiring con- 
siderable doses in order to act, cannot be introduced, because the 
quantities would be beyond the capacities of the cellular tissue. 
This also applies to alimentary substances, which could only be 
introduced in such minute quantities as to have no perceptible 
effects. 

Medicaments, such as oily bodies, which are not of themselves 
soluble, will not find, in the cellular tissue, the necessary elements 
to effect their dissolution. There are other substances which can 
only be dissolved by the aid of acids; oxide of zinc is soluble 
in hydrochloric or sulphuric acids ; and the chlorides of zinc are 
irritating and caustic substances, which, consequently, cannot be 



206 PKINCIPLES AND METHODS OF THEKAPETJTICS. 

introduced under the skin. There are other substances which are 
directly soluble, but very irritating, like phenic acid, creosote and 
perchloride of iron. These cannot be introduced by the hypo- 
dermic method, because they would cause phlegmons. 

There are again substances which cannot be thus introduced 
by the subcutaneous method, because they should be taken with 
the food. Such are those which either become soluble during 
the digestive process, or require being mixed with the chymous 
mass so as to come into the circulation with the aliments them- 
selves; these are the medicaments which have been named 
eutrophics, which I have called histogenics, that is, which help 
in forming histological elements, for instance, the calcareous phos- 
phates, cod-liver oil, and even iron, which is likewise an aliment 
properly so called. Alteratives, like certain arsenical prepara- 
tions, should be taken at meal-time. This hour has also been 
recommended for taking preparations of phosphorus, because 
they are better assimilated under those conditions. 

Finally, when you desire to exert a topical action upon some 
mucous membrane, as that of the respiratory, or especially of 
the digestive organs, you will certainly give your preference to 
introduction by inhalation in the first case, and through the 
stomach in the second. And here there is a peculiarity which is 
interesting to know. 

There are two kinds of emetics, as I have long ago estab- 
lished, and as I again recently stated before the Academy of 
Medicine. There are emetics . which act on the periphery, on 
the distal extremities of the nerves of the stomach, and the 
par vagum, or else on the nervous extremities of the branches 
of the solar plexus ; but there are others which, on the con- 
trary, act on the bulb. The first act after the manner of an 
indigestion ; the second like a meningitis. Apomorphine is the 
type of this last category of emetics. According to all ex- 
periments, it seems to act upon the central nervous system 
while exerting its influence upon the bulb. 

But the majority of other emetics, tartar emetic itself, and 
especially the emetics derived from the vegetable kingdom, act 



HYPODERMIC INJECTIONS. 207 

directly on the stomachic and intestinal mucous membranes. 
These last, as also ipecac, and all plants of an emetic character, 
seem to act directly on the gastro-intestinal mucous membrane. 
The proof of this is easily given : When emetine is introduced 
hypodermically, it requires 20 to 30 centigrammes to produce 
effects, which are longer in appearing and less intense than those 
obtained by a smaller dose given through the stomach. And 
what is curious, when this experiment is made upon animals, 
and they are killed, the emetine is found in the digestive tube. 
This shows that when introduced into the cellular tissue, it had 
first to be absorbed, then circulate and be brought by the arterial 
blood into contact with the organs it excites when given through 
the digestive apparatus; and it is only after having been secreted 
in sufficient quantities in the digestive tube that it commences 
to produce its effects. Therefore, it is best not to use the hypo- 
dermic method when you desire to bring on vomiting or nausea. 

Among the inconveniences attending the hypodermic method, I 
may add, that its application generally requires the physician's 
intervention. In the majority of cases, neither patient nor 
attendants can be entrusted with the performance of the operation 
without assuming undue risks of accidents. 

In conclusion, I may say that the hypodermic method dis- 
tinguishes itself from all or nearly all others, by qualities of 
such striking importance, that in a majority of cases they over- 
balance all disadvantages which the method may otherwise pre- 
sent. It offers us rapidity of action, constancy, and great inten- 
sity and absolute security as far as physiological and therapeutic 
effects are concerned, since we are certain that all we wish to 
introduce has been introduced. Besides, by the aid of exact 
doses we arrive at a degree of preciseness which it is impossible to 
attain in any other way. Upon the whole, it is really a scientific 
method, and one which should always be resorted to when 
applicable. Recourse should be had to it when the effects of 
different substances are to be measured, and it is, thanks to it, 
that such precise and conclusive results have been arrived at, as 



208 PRINCIPLES AND METHODS OF THERAPEUTICS. 

those obtained by Frazer, in England, with the principal alka- 
loids and their reciprocal actions. 

I have now to mention another method of introduction — that 
through the deep cellular tissue, the deep-seated organs, and the 
lymphatic ganglions. This method of introduction into the 
very depth of organs has, of late, attracted attention, but, not- 
withstanding, is not of recent date. 

Some fifty years ago acupuncture was borrowed from the 
extreme east and introduced into medicine ; electricity was subse- 
quently added to it, and this formed electro-puncture. I remem- 
ber when this method was still in favor ; I have inserted pla- 
tinum needles in the thighs of persons complaining of sciatica, 
and I have done so under the direction of my illustrious teacher, 
Lallemand, of Montpellier. Mr. Julius Cloquet wrote a book,l 
setting forth the merits of this method, not only according to 
the reports of foreign physicians, but also from observations 
made by himself. 

About that period Fabre, knowing certain facts connected with 
electricity, conceived the idea of applying it for the purpose of 
introducing active substances into the deep structures of a limb. 
A platinum needle is passed into the structure deep enough to 
reach the desired spot, and placed in communication with a bat- 
tery containing a solution, say of sulphate of copper. If the 
needle is connected with the negative pole, that pole will trans- 
port the electro-positive substances attracted to it; the substance 
and its effects will therefore be carried into the depths of the 
limb. On the contrary, if the connection is made with the 
positive pole, the reverse will take place — the substances com- 
posing the solution, and acting the part of electro-negative bodies, 
will be transported and attracted to the positive pole. We shall, 
therefore, find on that side, for example, iodine, chlorine, arsenic 
and phosphorus. 

Fabre applied this method in cases requiring the resolution of 
chronic congestions, and in some instances met with good results. 

The method is now quite abandoned, yet there are cases in 

Cloquet. A Treatise on Acupuncture. Paris, 1826. 1 Vol. 8vo. 



ELECTRO-PUNCTUKE. 209 

which it might perhaps be utilized. For example, to destroy 
uterine myomata, substances might thus be introduced into them 
capable of bringing about their necrosis. The method was 
given up on account of its difficult application, and also because 
the current did not always transport active substances. We now 
have improvements over the former instrumental appliances 
which might remedy these defects. Of late years that method 
has been replaced by another, which is allied to hypodermic in- 
jections in so far that a somewhat enlarged Pravaz syringe is 
used with it. Its author, my former disciple, Professor Lutton,! 
of Rheims, having to deal with a number of cases refractory to 
ordinary processes, as for example, those enormous lymphatic 
ganglions of the neck which extend into the interior of the 
thoracic cavity, and against which everything fails, thought the 
patient might be relieved if by some process those tumors were, 
if not removed, at least dissolved. 

For this purpose, he introduces a canula, or a slender explor- 
ing trocar, into the tissue to be modified. He then watches the 
fluid evacuated, and according to its nature, decides whether or 
not it is advisable to apply the injection which is to modify the 
diseased organ, either by producing a more or less violent inflam- 
mation, or by simply determining changes in its sensibility or its 
nutrition. Strictly speaking, this method hardly comes within 
the limits of my subject, because it has not as an object the in- 
troduction into the circulation of substances intended to produce 
diffused effects. Nevertheless, as, in a number of cases, the sub- 
stance does penetrate into the general economy, and as this 
method is a sort of annex to the hypodermic one, I deem it 
advisable you should be made acquainted with it. 

Phenomena of irritation, even of more or less advanced 
phlogosis, with suppuration and sometimes gangrene, are liable 
to follow. Alcohol, more or less concentrated tincture of iodine, 
bichloride of mercury and nitrate of silver are chiefly used. Dr. 

1 Lutton. A Treatise on Subcutaneous Injections for the Purpose of Pro- 
ducing Local Effects. Paris, 1875. 



210 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Lutton seems inclined to attribute all the effects attending these 
different substances to substitution. 

I never forego an opportunity of condemning this expression, 
because it is not scientific and has been the cause of great con- 
fusion. 

Trousseau called this process of substitution a homoeopathic 
action. The homoeopathists took advantage of this, and always 
mention Trousseau as having been one of their number. Vainly 
did he protest, claiming only to have said that it was but another 
inflammation replacing the first, and carrying away the first 
irritation by the aid of a greater excitement. I will show 
you that that expression was doubly unfortunate, since it did not 
even define a scientific idea. 

For example, chloride of sodium is injected into a region in 
which there exists a pain, and they say chloride of sodium pro- 
duces a sharp pain which is substituted for the former one. This 
is all wrong ; they should say chloride of sodium causes a very 
rapid irritation, and by means of this, which is not lasting, a sort 
of nervous exhaustion takes place, exactly as is the case with per- 
sons suffering from shock after accidents. It is what Dupuytren 
termed a nervous bleeding. But the pain which momentarily dis- 
appeared soon returns. 

Tincture of iodine resolves congestions ; it is the substitution 
of an acute for a chronic inflammation. Of course, an inflam- 
mation has been excited; but is this all? Iodine, in small 
quantities, acts as a resolvent ; and in large quantities, as an in- 
flammatory agent. Either of these effects may have contributed 
to the disappearance of the tumor. But that is no substitution. 
With nitrate of silver it is the same; it substitutes nothing, but 
it produces an eschar in the depths of the organs in which it is 
deposited, and this eschar is eliminated through the process of 
suppuration. A similar process has been long in use. By the 
aid of a red-hot iron, or by means of a cautery, purulent issues 
and consecutive resolutions have been determined ; consequently, 
as you see, there is no occasion for using the word substitution in 
cases pertaining to this method. 



PARENCHYMATOUS INJECTIONS. 211 

The professor from Rheims, who has advocated these injec- 
tions, had been anticipated. I will not speak of Nekton, who 
introduced a few drops of alcohol into furuncles for the purpose 
of aborting them. This rather belongs to the entodermic method; 
but Jobert de Lamballe has already suggested the introduction 
of a few drops of tincture of iodine into the epididymis when 
congested. Injections in the serous cavities, as in the vaginal 
folds, may be added to the above examples of antecedence to 
Lutton. Still, we must give to the professor from Rheims the 
credit he deserves. He has gathered all these facts into a gen- 
eral method, and in a number of cases has obtained interesting 
results. It is true that in others they have been null or regret- 
able, and as a rule illusive. 

Parenchymatous injections have been used in cases of obstinate 
neuralgias, and especially against sciatica. We tremble, a priori, 
at the idea of introducing in close proximity to the sciatic nerve, 
at least when impaired in its functions, such substances as a con- 
centrated solution of nitrate of silver, capable, as it is, of pro- 
ducing a phlegmonous inflammation. No doubt nitrate of silver 
and the other more or less caustic substances introduced by 
Lutton and others, have caused suppurative phenomena in the 
deep-seated cellular regions, but fortunately the course of the 
needle itself has supplied an outlet for those products of inflam- 
mation. When this course has become closed, accidents have 
happened ; but it usually remains open, because in withdrawing 
the instrument there are always a few drops of the caustic solu- 
tion which remain in its path. In this case, after a few days, 
more or less serous or purulent secretions are evacuated without 
causing any great damage to the nerve in whose proximity the 
inflammation is seated. It is, thanks to this circumstance, that 
more serious accidents do not often happen. At all events, I 
have placed you on your guard against illusions which have been 
indulged in by able men. The relief is but momentary ; after a 
short time the neuralgia returns the same as ever. I have had 
occasion to witness this in the case of one of the most eminent 
men in the medical profession who, against my advice, insisted 



212 PRINCIPLES AND METHODS OF THERAPEUTICS. 

upon having injections of nitrate of silver made upon himself. 
They produced abscesses, but absolutely no advantage from a 
therapeutic point of view. 

I have now reached the last among the avenues of introduction. 
It is that through the vascular system, and particularly through 
the veins, as being the least dangerous method. 

This method of introduction is already over two centuries old, 
the first injection in the veins having been made in 1665. There 
are even traces of much older instances than this. Verses from 
Ovid seem to indicate that he knew of the practice, or believed 
in the possibility of intravenous injections, and particularly of 
transfusions of blood, for he says : 1 " Take from me this old 
cruor, that I may fill my emptied veins with youthful blood." 

Probably this is nothing more than a poetic image, but there 
is an instance which seems more authentic, and which takes us 
back nearly four centuries. It is the case of Innocent VIII., 
who having fallen into a state of marasmus, called in a Jewish 
physician, who conceived the idea of transfusing blood into his 
veins. The blood was procured from three little boys, who died, 
probably because too much was taken from them. This opera- 
tion took place in 1492, the year in which America was discov- 
ered. The operation did not save Innocent VIII. from death, 
and lost the three children, so the Jewish doctor was obliged to 
flee for his life. 

It is also said that in 1615 Libavius, whose name is celebrated 
in chemistry, practiced transfusion, but this is not certain. 

In 1665, a really scientific period commenced at Oxford, 
where the idea was first had of infusing medicaments in the 
veins of animals. That proposal was made to the Bishop of 
Exeter, who adopted it; we must suppose that at that time 
bishops were not members of the society for the protection of 
animals. This gave rise to the idea that medicaments, and blood 
even, could be injected into the human veins, and is the starting 
point of the method as known to us at the present day. 

1 " Ut repleam vacuas juvenile sanguine venas." Ovid, Metamorphosis. 
Lib. VII. 



TRANSFUSION OF BLOOD. 213 

In 1665 Lower practiced the first transfusion of blood. He 
was closely followed by Kaufmann, in Germany. At one time, 
judging from the resul-ts announced, it seemed as if the secret 
of perpetual youth had been discovered. But a number of acci- 
dents happened, and the Parliament of Paris passed a resolution 
surrounding this operation with a number of guaranties, which 
were a credit for the doctors of that period ; it was necessary to 
be a doctor of the faculty of Paris in order to have the right of 
practicing it. But the operation soon fell into disuse, and it was 
only in 1818 that it again re-appeared. 

It was applied to animals by Messrs. Prevost and Dumas, and 
by Magendi, in 1823. Since then numerous transfusions have 
been made. I shall first speak of these, and will then dwell on 
medicamental infusions. 

What fluid should be injected ? Everything has been tried — 
serum, globules and more or less well-dissolved hemoglobine. 
Trials have been made with natural blood, and with blood nearly 
so, but stripped of its fibrine. We shall review these different 
ways of effecting transfusion, and judge their results. 

Let us begin with serum ; it only gives illusive or harmful 
results. At first sight, it would seem advantageous to introduce 
it, since it is an aliment, containing albumen in considerable pro- 
portion, fibrine, and all the salts naturally contained in the blood. 
But in Prevost's and Dumas' experiments, serum has never given 
any results — it has never prevented animals from dying — and 
Dieffenbach's experiments confirm theirs. Moreover,, it is harm- 
ful. It has been observed that 300 grammes of serum intro- 
duced into a dog produce nervous convulsive phenomena, a sort 
of delirious agitation, followed by collapse and death in twenty- 
four hours. 

The conclusion, therefore, is that if any benefits are to be de- 
rived from the transfusion of blood, we must not have recourse 
to serum. 

Hemoglobine has been injected without producing -any good 
results. I may even say it is harmful, in proportion to the 



214 PRINCIPLES AND METHODS OF THERAPEUTICS. 

quantity in which it is introduced. Mr. Paul Bert 1 considers 
heinoglobine, when alone, more as a poison than as an agent of 
respiration. 

As to the globules, it is evident that if they could be intro- 
duced one at a time, without any difficulty, they would produce 
considerable activity in the great functions. But they have to 
be introduced by the aid of liquid substances. Must this liquid 
be the serum, or is it advisable to deprive it of part of its ele- 
ments, and of the fibrine in particular ? 

Let us first settle a previous question. Blood should be intro- 
duced in its complete state, or nearly so, but it must be liquid. 
You know that blood coagulates ; therefore, what is the best way 
of keeping it in a fluid state ? 

These ways are numerous. In the first place, it has been ob- 
served that a low temperature keeps blood in a fluid state for a 
long time ; Dieffenbach mentions three hours when in a refriger- 
ant mixture. Unfortunately this iced blood cannot be intro- 
duced in the veins without the most deplorable consequences. 
Therefore, our only recourse is to receive the blood in vessels 
heated to a temperature of -|- 37° or ~\- 38°, which is nearly that 
of the animal supplying it. By this process blood remains fluid 
for about forty-five minutes ; this gives ample time to inject it, 
especially if a given quantity of neutral salts are added to the 
blood. 

1 Paul Bert. Lessons on the Comparative Physiology of Eespiration, 
page 88. Paris, 1870. 



TRANSFUSION OF BLOOD. 215 



CHAPTER XIX 
Transfusion of Blood — [Continued.] 

Different methods of transfusion. — Apparatus. — Expected effects of injected 
blood. — On the selection of blood, whether arterial or venous, animal or 
human. 



Gentlemen : 

In our last lesson I mentioned the use of neutral salts for the 
purpose of preventing the coagulation of blood. Phosphate of 
soda, and carbonate and nitrate of potash, are the salts generally 
used ; they are taken from the blood serum itself, and really 
prevent coagulation. But nitrate and carbonate of potash are 
objectionable, because they have a poisonous effect, and Pavie 
has proven that, in a great number of circumstances, blood kept 
fluid by means of these salts has acted toxically upon animals. 
They have, therefore, been abandoned. 

Sulphate of soda is chiefly used. Prevost and Dumas have 
employed it in doses of 14 per 100, and even per 1000, and it 
has proven itself an efficient obstacle to coagulation. But in 
small doses it hastened coagulation, hence it had to be used in 
large quantities, and has therefore been given up. 

It was then suggested that the blood should be defibrinated. 

At first thought this method strikes one as irrational, because 
blood being an aggregate, the globules cannot be isolated from the 
fibrine and the plasmine without suffering great damage, and, 
consequently, endangering the success of the con tern pla ed opera- 
tion. Hence, this process has, from the first, been denounced by 
able men. 

Magendi pronounced against it by saying that natural blood, 
retaining all its principles, was alone capable of sustaining life. 
Poiseuille also said that without its fibrine, blood could not be 



216 PRINCIPLES AND METHODS OF THERAPEUTICS. 

of any service. Desgranges and Devay maintained that globules, 
when beaten, are as good as killed; Giraud-Teulon also pre- 
ferred the whole blood. Roussel, of Geneva, who, of late years, 
has even made a scientific tour for the purpose of establishing the 
great importance and efficacy of his method for the transfusion 
of blood in the veins, has likewise declared that the failure of a 
certain number of operations, apparently under favorable circum- 
stances, was due to the fact that defibrinated, that is, a bad qual- 
ity of blood, had been used; finally, my regretted colleague, 
Behier, in his picturesque language, exclaimed that blood beaten 
to death was blood which, henceforward, should never be used. 
Still the contrary opinion for a long time prevailed, and does 
yet in the minds of a number of practitioners, among whom we 
find many illustrious names. 

Messrs. Prevost and Dumas were the first to use defibrinated 
blood. They observed that this blood contained, apparently, 
unbroken globules, which retained not only their form, but also 
their chief properties. These observations have, of late, been 
confirmed by my friend, Prof. Brown- Sequard, who has made on 
this subject, experiments that appear conclusive. He saw that 
the globules of defibrinated blood had lost their aspect, their 
conformation, and their dimension ; but they reddened when in 
contact with oxygen, and grew black under the influence of car- 
bonic acid. He observed that when introduced into the veins 
of bloodless subjects, who were at the point of death, they pro- 
duced the same physiological effects he had demonstrated belonged 
to arterial blood, that is, a very evident excitation, not only of 
the nervous centres, but also of the contractile fibres, either of 
relative or organic life. For example, they excite the movement 
of the intestine and awaken the respiratory functions, which cir- 
cumstance illustrates the physiological action of the substance 
used. Hence, these experiments seemed to justify the idea of 
defibrinating blood. I must add that a long series of cases could 
be appealed to, in which the injection of defibrinated blood had, 
apparently, given good results. If, on the one hand, we consider 
the physiological experiments, and, on the other, the therapeutical 



TRANSFUSION OF BLOOD. 217 

results, it is difficult not to admit that this process is good in 
itself, and that it probably answers all practical purposes 

Yet, such is not the case ; in experiments and observations all 
coincidences should be laid aside. There are many cases in which 
an animal, even when exsanguine and at the point of death, 
returns, unaided, to life. 

According to Mr. Vulpian, this circumstance renders all con- 
clusions very difficult, because, even when three-fourths of an 
animal's blood has been withdrawn, it may yet survive. But 
here a great number of positive facts may be called up, which 
form a series of lamentable failures. That is, where, in the 
midst of favorable conditions, and when the injection into the 
veins should have restored life, it has been seen to pass away 
without recourse. These unfavorable cases are in greater num- 
ber than when blood, in its natural state, is used. 

Another point to be noticed is, that not only is the method 
useless, but it is even haimful. It has been observed, in a num- 
ber of cases, both among animals and men, that the introduction 
of this defibrinated blood, has given rise to serious, grave, and 
really poisonous phenomena, consisting in nervous movements, 
convulsions, and, finally, in death. These phenomena were, evi- 
dently, in proportion to the quantity of blood introduced ; with 
men, they showed themselves in less marked form; but they 
were fully displayed among animals, with whom a more liberal 
quantity of blood had been used. 

Moreover, it might have been thought that by defibrinating 
the blood, by only leaving the serum and the globules, we would, 
at least, have been secure against accidents from emboli; this is 
not the case, however, and Mr. Vulpian told me that in a num- 
ber of experiments made by him, he had, on the contrary, found 
that thrombi had often been the cause of the animal's death, in 
whom these injections had been made. The reason of this is, 
that although care has been taken to strain the defibrinated blood, 
so as to avoid the clots, it is impossible to guard against those 
which, although invisible to the naked eye, are yet of considera- 
ble importance when we consider the calibre of the least order of 



218 PRINCIPLES AND METHODS OF THERAPEUTICS. 

capillaries. These little grumes are enough to produce capillary 
emboli, and, consequently, accidents of comparative gravity, if 
these infarcts are numerous. I must add that even in cases where 
results were favorable, they were not lasting. 

The re-animation of the organism in which the injection had 
been made, was shorter than with blood in its natural condition. 
These results could have been foreseen, and so they were, by 
physiologists. 

For my part, I was convinced such would be the case, because 
the globules are not only suspended in the serum, but each one 
is surrounded by an atmosphere of plasmine ; if the number of 
globules in the blood is reduced, the proportion of plasmine 
becomes excessive ; it is then free, and capable of being elimi- 
nated through the emunctories, which serve as passages for the 
protein ous matters. For this reason, when the number of glob- 
ules in a patient becomes reduced, albumen shows itself in the 
urine. In a word, the globules seem to be a centre of attraction, 
around which certain portions of albumen congregate. The 
removal of this plasmine endangers the nutrition and life of the 
sanguineous globules. Everything, at present, concurs in pr*>vkig 
this to be the correct view. 

When blood in its natural state is used, we are met by all the 
objections urged against coagulation. But now, thanks to an 
improved apparatus, blood drawn from a vein is so rapidly in- 
jected, that it has neither time to coagulate nor to mix with air. 
It is true that only venous blood can be thus introduced, but we 
shall presently see that this is no unfavorable condition, and that, 
in fact, it is a matter of indifference whether venous or arterial 
blood is used. 

In the instrument invented by M. Collin, the blood is 
received in a cupule, which has first been heated by means of 
hot water to a temperature of about 38° (blood is at + 37.5°); 
this temperature remains about constant while the operation 
lasts ; the cupule is connected with a pump-barrel for the pur- 
pose of injecting the blood. The improvement in the instru- 
ment consists in this, that the cupule and pump-barrel are con- 



TRANSFUSION OF BLOOD. 219 

nected by a tube in which there is a little aluminum ball, whose 
specific gravity is less than that of water, and, of course, much 
inferior to that of blood. When blood is poured in the cupule 
the ball rises, and communication is established with the pump ; 
as blood is withdrawn, the ball descends and prevents the air 
from penetrating along with the blood in the pump-barrel. 

This apparatus is of great simplicity and easily handled. By 
its aid, not only is the necessary quantity of blood readily drawn 
from the vein of the one supplying it, and we shall see that for 
the purpose of awakening life in a person at the point of death, 
this quantity need not be large, but the blood is rapidly injected 
without carrying with it any of the gases that might favor 
coagulation, and what is of vast importance, without any air 
being introduced into the veins. 

Let us now examine this question from a scientific and prac- 
tical point of view, and understand the part acted by the blood 
in its natural state when injected into the economy. 

It has been said by some that it acts only as a stimulant, 
others claim that it is a real life-regenerator ; probably, as is 
generally the case, the truth lies between the two extremes. 

But, in the first place, I would have you remark that blood in 
its natural condition, such as we at present introduce, has three 
parts to perform. 

In the first place it brings nutriment. In the case of an ex- 
sanguineous individual, who not only has lost globules, but also 
all protein matters intended to maintain the nutritive integrity 
of all the organs, injected blood supplies him with plasmine 
and the elements of chyle. 

In the second place, blood also brings oxygen, which favors 
combustion, but this is not always the case, because it is mostly 
venous blood which is introduced. 

In the third place, it especially carries globules, which are the 
principal agents of hematosis and the nutritive phenomena. The 
blood globules are a vehicle for the gases, they bring oxy- 
gen into the organs, and carry away carbonic acid, and by means 



220 PKINCTPLES AND METHODS OF THEEAPEUTICS 

of this exchange calorification, and therefore nutrition, are 
maintained in action. 

Besides, as I previously stated, the globules are necessary cen- 
tres of attraction in order that the blood may preserve its normal 
constitution ; from the moment they so decrease in number that 
a large proportion of the plasmine is set free, serious suffusions 
are everywhere formed and create a new source of danger to 
life. 

You may urge that defibrinated blood supplies all these 
wants ; but I will now show you that it does not. 

Defibrinated blood supplies dead or dying globules, which still 
retain the property of absorbing oxygen and carbonic acid ; they 
are able, for a short time, to perform the functions of globules, 
provided their structure is not impaired. As I stated, when 
globules are deprived of plasmin, their vitality is impaired, and 
this explains how, in a number of cases, results have been so 
instantaneous, and why, in others, toxical phenomena have fol- 
lowed. These latter are very easily understood since the experi- 
menis made by Paul Bert, because we know that when a large 
quantity of impaired globules, or natural hemoglobine, is intro- 
duced into the circulation of an animal, not only does it derive no 
benefit from the treatment, but it may become poisoned, and even 
be killed. There are also cases in which a large dose of such blood 
in the human system has produced real toxical accidents ; even 
paralysis and death. At all events, as I remarked, it is only for 
a very brief moment that these perishing globules are able to 
continue the functions incident to their structure, for, as I have 
had frequent occasion to point out to you > the organic properties 
belonging to structure are independent of life ; life may become 
extinct in an organ, and that organ may still conduct a nervous 
current, or else contract itself under the influence of excitants. 
In the natural blood, which has lost none of its indispensable 
constituent elements, and which has retained not only its serum, 
but also its plasmine, the globules preserve their vitality, 
and consequently their effects are far more lasting than those of 
globules taken from defibrinated blood. The continuance of 



TRANSFUSION OF BLOOD. 221 

these effects, however, is not unlimited, because, while we do not 
know the duration of globular life, we have reason to believe 
that it does not extend beyond a few days — nay, perhaps not 
over a few hours. But a few days of functional activity commu- 
nicated by the introduction of new blood, may be the means of 
saving life in a great number of cases. 

Now, the question is, have the globules in new blood the 
power to determine the formation of native globules in the 
blood into which they have been injected ? In other words, when 
new globules are introduced in an exsanguine animal or in a 
woman who has experienced profuse hemorrhages during labor, 
have they the faculty of developing, jproprio motu, other globules, 
or of favoring their development ? By some this is unhesitatingly 
answered in the affirmative ; for my part, I believe new blood 
can indirectly favor the generation of red globules in the organ- 
ism into which it has been infused, but it is doubtful whether 
this is directly possible ; in fact, it may even be looked upon as 
impossible, because globules are not reproduced by fissiparity. 
Hence they can only act indirectly as a stimulus to the organism, 
and consequently to formation and nutrition. 

Nutrition, and the recruiting of organs already formed, is a 
similar phenomenon to that of fecundation, according to the 
revelations of Aristotle and of my teacher, Lallemand. There- 
fore I say that by means of this stimulating influence, exerted 
over a failing organism, it is possible that these globules favor 
that formation. They may even contribute towards it in another 
way, because we know that organs are formed under the influence 
of particular conditions ; hence, from the moment that these 
conditions are present, the genesis of these organs will take place 
in a more active way. 

We know that the blood globules are not formed in the blood. 
I am inclined to think they originate in the lymphatic system, 
but in order that they may acquire their development the presence 
of a certain number of blood globules is necessary. I have long 
ago advanced the opinion — and the subsequent development of 
certain theories in Germany lead me to believe I was in the right 



222 PEINCIPLES AND METHODS OF THEKAPEUTICS. 

— that a communication exists between the lymphatics and the 
veins, and that the object or effect of this communication is the 
introduction into the lymphatic system of blood globules, which 
act the part of allurements or suggestions for the formation of 
new globules. In this way we can understand that when glob- 
ules are injected, they may be able to favor the genesis of other 
globules. We should also take into consideration the influence 
exerted by the power of numbers. 

JSTow that we know what may be expected from blood in its 
natural and intact state, when injected into the veins of subjects 
requiring globules, let us ascertain whether arterial or venous 
blood should be selected. On this subject the greatest differences 
of opinion exist among writers. 

There are those who insist upon arterial or arterialized blood. 
Others, on the contrary, are content with venous blood, and a 
few, even, give it the preference. In order to discover which 
opinion is correct, let us first examine the real differences exist- 
ing between the two bloods. My friend, Brown-Sequard, has 
long ago fully settled this point. He has shown that arterial 
blood is best for the purpose of increasing the vital energy of 
the organism. Let me borrow from the old medical nomencla- 
ture a very correct and expressive phrase : Arterial blood in- 
creases radical force. Not acting on the nervous system, it does 
not awaken that complication of symptoms which I have de- 
scribed. It is a way of increasing the vital energy. 

According to the same author, venous blood is, par excellence, 
a stimulant. It gives rise to all the functional manifestations I 
have mentioned, but, on the other hand, it does not increase 
strength, nor the real vital power. It therefore calls into activity 
the functions, when these are more or less languid. 

In other words, while arterial blood increases the radical forces, 
venous blood seems to augment the acting forces. This is also a 
distinction I have endeavored to establish between continuous and 
interrupted electric currents. A continuous electric current is a 
means by which the organs can be charged. An inductive cur- 



TRANSFUSION OP BLOOD. 223 

rent is a way by which to excite them. I have already given 
you illustrations of this theory. 

It seems difficult to establish a choice between arterial and 
venous blood, equally urgent reasons recommending them to ex- 
perimenters. Brown- Sequard decides in favor of venous blood, 
because it is a stimulant. He believes it should be introduced, 
as it has the power of awakening the functions of the respiratory 
and circulatory apparatus, and that it is through those that 
animals and also human beings perish when they have suffered 
very heavy losses of blood. However, Bischoff, in his experi- 
ments, has noticed that venous blood kills an animal more rap- 
idly than arterial blood taken from another animal. That is, for 
example, if the venous blood of a sheep is introduced into a 
goose, it will die quicker than if arterial blood had been used. 
This proves nothing, except that birds have a mean temperature 
equal to the maximum or pathological temperature of other 
animals, consequently combustion in them is very active, and 
therefore they perish sooner when deoxidized blood is injected 
into them, than when blood is introduced which is still capable 
of momentarily galvanizing their organism. Hence, Bischoff's 
experiment is of but little value against the use of venous blood. 
Nevertheless, a great many writers give the preference to arterial 
blood, basing themselves upon the knowledge we have of the 
usefulness of oxygen in respiration, and consequently in the 
whole functional action. They contend that under all circum- 
stances it is best to introduce into the organism blood laden with 
oxygen, because during the course of circulation this gas will 
determine all the effects of combustion, and consequently will 
more readily awaken an organism undergoing destruction. 
Evidently this view is a very correct one. But let me remark, 
that when we make a transfusion upon a man, we do not intend 
to galvanize his system, but we desire to bring to him powers 
that have persistence, that will live a given length of time, and 
that are able to keep up the functions in the patient as long as 
necessary, and until he is once more able to form globules. 



224 PRINCIPLES AND METHODS OF THERAPEUTICS. 

"Coder these conditions it is of little importance whether at the 
start the blood used is charged with oxygen or carbonic acid. 

In the first place, arterial blood cannot be procured without 
much trouble, for an arteriotomy can only be performed on an 
animal and not on a man. However, to this there is one ex- 
ception. I have seen my teacher, Trousseau, perform arteriotomy 
on the temporal artery, that is, on an artery resting on a resist- 
ant plane, over which compression is easily effected. He per- 
formed this operation without any danger in cases of facial neu- 
ralgias resisting all other methods. (The operation would be 
censured at the present day, but at that time aconitine was un- 
known.) If arterial blood is required, it is from there it should 
be procured. Venous blood could be arterialized by being com- 
pressed with oxygen, or agitated with air. But this is a bad pro- 
cess. As I have told you, agitation favors coagulation, even if 
the mingling of gas with the blood had not the disadvantage of 
introducing air into the veins. 

Dr. Gesellius has invented a process for obtaining arterial 
blood, which he believes practical, but which is not. It consists 
in pumping the blood from the capillaries of some fleshy portion 
of the body. But the capillaries are not all arterial, and the 
blood thus obtained is in great part venous. This does not even 
answer its intended object ; besides, it is difficult to obtain thus 
the necessary quantity of blood in a sufficiently fluid state, not 
to cause emboli. 

Hence, as you see, on the one hand, the having arterial rather 
than venous blood is not of great importance ; and on the other, 
it could not be obtained without danger to the one supplying it. 
Consequently, venous blood has come into general use, and, while 
it does not supply strength, it at any rate produces stimulating 
phenomena, which probably, at the first moment, are of greater 
utility than strength itself. In fact, in a great many circum- 
stances, after serious traumatisms, the first requisite is to awaken 
the organic functions, stimulate the contractility of the cardiac 
muscle, and revive the functions of the circulatory system. For 
those purposes, therefore, it would seem that venous blood is 
preferable to arterial. 



TEANSFUSION OF BLOOD. 225 

Humboldt favored the use of blood laden with chyle, because 
an exsanguine individual is incapable of digesting, and by that 
means he would be supplied with blood and aliments which he 
otherwise could not procure. If the use of animal blood was a 
matter of indifference, I might be in favor of feeding an animal 
and taking its blood while laden with chyle ; but we cannot ask 
a man to imperil his life by giving his blood during the process 
of digestion, when we know that blood-letting, under those cir- 
cumstances, is highly dangerous. Therefore, this is a method 
which cannot be applied, and it is of but limited utility as an 
adjuvant when an object is simply the introduction of globules. 

We are here met by a very serious question, which is, whether 
the blood of animals can be employed, or should we limit our- 
selves to the use of human blood ? In the early stages of the 
method the blood of animals has been used, and Denys reports a 
number of examples which indicate that this has been done with 
safety. But I will show you that it is not absolutely devoid of 
danger, and that it is best only to use human blood. 

p 



226 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XX. 
Transfusion of Blood— [Continued.] 

Quantity of blood to be introduced. — Manner of operating. — Who should sup- 
ply the blood. — Venous transfusion. — Mediate and immediate effects of 
transfusion. — Indications and counter-indications. 



Gentlemen : 

At first thought it would seem that in order to restore the 
regular functions of a depleted organism, it would be necessary 
to return to it the full measure of blood lost. This, however, is 
not the case. Small quantities are sufficient to produce re-anima- 
tion j larger doses would be superfluous, and very large doses 
would really prove toxical. 

When very large quantities of blood are introduced into ani- 
mals, they produce accidents of a nervous nature, troubles in the 
motor and sensory systems, and real convulsions, which may re- 
sult in " sideration," according to the sense now given to this 
word, and finally end in death from a sort of rapid syncope. 

These phenomena may be explained in two ways. In the 
first place, by a sort of traumatism, for Waller has proven that 
when a quantity of new blood is introduced, the vascular system, 
which was already distended, suddenly develops such an amount 
of resistance that serious accidents immediately follow, caused 
simply by mechanical effects. It is said that under such a shock 
the heart ceases beating. But besides this vascular repletion and 
all the accompanying phenomena, there is also a state of real in- 
toxication, which results from an accumulation of the products 
of globular denutrition in the blood of the individual receiving 
the new blood. The effects of this blood are not those of real 
poisons, but, as you know, whenever the economy is burdeued 



TRANSFUSION OF BLOOD. 227 

by any kind of refuse from denutrition, the organic functions 
become seriously impaired. These are what I have called cases 
of passive poisoning. For example, when there are large quan- 
tities of urea in the blood, if it becomes an obstacle to organic 
renovation, after a time the old and worn-out organs are no 
longer able to fulfill the requirements of the organism and the 
patient dies. The same phenomenon takes place upon the intro- 
duction of a large quantity of new blood. Its globules not being 
long-lived, finally become an encumbrance to circulation, and 
in consequence are a cause of reduced activity for all the functions, 
in place of being the cause of stimulating and even vitalizing 
effects. 

Very copious injections can, however, be made. Mr. Richet 
succeeded in introducing 1000 grammes of blood into the body 
of a human subject, but this was done with extreme slowness, so 
that each dose introduced could not produce either the mechan- 
ical or the general serious effects of which I just now spoke, and 
which are the result of a species of intoxication. 

But we need not occupy ourselves with the effects attending 
the injection of a large volume of blood, since a small quantity 
is sufficient to produce a satisfactory result; and the re-animative 
power of a small proportion of blood seems to be so great, that 
a very moderate quantity appears quite sufficient. As an illus- 
tration, here are some figures : Desgranges and Devay have 
injected 180 grammes; this is a great deal — it is a. maximum dose. 
In other instances, 90, 80, 75 and 60 grammes have been in- 
jected. In two cases recorded as successful, 7 or 8 grammes of 
defibrinated blood were used. These are all very moderate doses. 
In other cases, we are told of 120 and 730 grammes; and, finally, 
Mr. Richet injected 1000. 

Taking into consideration the last transfusions which have 
been made, we shall find that a dose of 100 grammes has not 
been exceeded, and yet good results have been obtained. The 
same may be said of the cases reported by Briquet, Dolbeau, 
Maisonneuve, Lorain, Brouardel, Maurice Raynaud, Fereol and 
Straus, which have all been successful. As you see, the doses 



228 PRINCIPLES AND METHODS OF THERAPEUTICS. 

are not large ; the maximum injected has been the 5th, at times 
the 50th, and, most frequently, the 500th part of the total mass 
of the blood. Consequently, transfusion may be successfully 
accomplished without having at one's disposal, a very considera- 
ble source of blood. 

With regard to selecting the person who is to supply the blood, 
we should, as far as is possible, choose a young, healthy and vig- 
orous man ; and, in general, at the present day, there is no trouble 
in finding those who are ready to contribute their blood for the 
relief of others. 

Let us now consider the choice of a vessel, and the necessary 
preparation for the operation. Here, again, we are met by a 
double series of processes. As a rule, an intravenous injection 
is made, and as the blood is taken from a vein, it is " venoso- 
venous." Of late years, it has been thought best to do away 
with the use of an instrument, and to inject the blood directly 
into the circulatory system of the one who is to receive it. This, 
however, would require that the blood should be taken from an 
artery whose propulsive force could cause the blood to penetrate 
into the patient. 

Mr. Roussel has traveled over Europe for the purpose of 
establishing the efficacy of this method. In this process the 
arterial blood is to be procured either from an animal or from a 
man. But how can any one assume the responsibility of opening 
a man's artery for the purpose of transfusing blood ? Therefore 
the arterial blood of an animal has to be resorted to. Here, 
however, there is a difficulty, for I have shown you that this 
blood does not give the same results as blood from an individual 
of the same species. Besides, why incur all these dangers, when 
the results are not any more successful ? 

Among 28 cases of venoso-venous transfusions, there have been 
10 deaths, 2 remained stationary, and 16 were followed by im- 
provement or cure. In other instances in which the arterial 
blood of animals has been transfused, the results have not been 
so satisfactory. This method is not any more successful than 



TRANSFUSION OF BLOOD. 229 

another, but is surrounded with dangers ; therefore it is not enti- 
tled to the preference. 

In venoso-venous transfusion, the use of an instrument is 
necessary, because direct introduction is very difficult. The 
basilic vein is generally chosen ; an incision parallel to the vein 
is made, and a ligature is placed above it. A V-shaped incision 
is made in the vein, and the canula, through which the 
injection is to be made, is introduced into the vein ; an intelli- 
gent assistant holds the vein upon the canula, and the operation 
is very simple. 

Plain and complicated instruments of all kinds have been 
used, but, of late, very simple apparatus has been chosen j in 
fact, much too simple, for, in a number of cases, an ordinary 
irrigator has been employed. Desgranges and Devay, and others, 
have used a hydrocele syringe, more or less modified ; these are 
very simple instruments, but, like all those in which agitation 
takes place, they afford no security against coagulation and the 
introduction of air into the vein. At present, in the way of 
easy and efficient apparatus, we have that made by Mathieu, and 
the one invented by Colin, which I described in the last lesson. 
Both are so practical that we need no longer hesitate at practic- 
ing transfusion whenever the operation appears necessary. 

Having chosen the one who is to supply the blood, and the 
region, the vein is prepared and the blood-letting takes place; 
next follows the operation. The blood is received as near as 
possible to its exit, so that the venous fluid has neither time to 
break its globules nor to coagulate before it enters into the 
funnel of the instrument. 

If the object is simply a stimulating effect, a momentary 
revival of the patient, then globules in defibrinated serum will 
answer the purpose. But if you look for lasting results, for a 
re-animating injection, which is to place the subject under favora- 
ble conditions for a return to life, in that case the blood must be 
natural, intact, and in possession of all its elements. Under 
those circumstances the liquid blood is received in the funnel of 
the instrument, and a given quantity, say from 100 to 150 



230 PRINCIPLES AND METHODS OF THERAPEUTICS. 

grammes is made to penetrate with due moderation. That 
quantity should not be exceeded ; but we must proceed without 
haste. When this is accomplished, the. instrument is with- 
drawn, and a dressing is applied the* same as after blood-letting. 

Objections of all kinds have, however, been urged against 
transfusion. Although, as I have shown you, the operation is a 
simple one, and when properly practiced is generally exempt 
from nearly all disadvantages, still faults, drawbacks, and even 
dangers have been laid to its account. 

It has been declared that no good results could be expected 
from transfusion, because the globules we each possess are pecu- 
liar to and can only serve the one individual. This was a pre- 
judice ; experiments made on a large scale prove that, in reality, 
transfusion produces very good results, which are not only 
immediate, but also lasting, and that it has been the means of 
saving a great many lives. 

It has been said there is danger in substituting the blood of 
one species for that of another. This is no doubt true in certain 
cases, but the blood of fishes has never been introduced into the 
veins of man ; use has been made of the blood of calves and 
other animals having small circular globules, which can cause 
no ill effects. 

The dangers of virulent inoculation have also been menti®ned. 
But these exist everywhere, even in vaccination. Instances are 
on record when vaccine matter has been a vehicle for syphilitic 
infection. All we can do is to be careful in the selection of a 
subject, and he who offers to contribute his blood must feel sure 
of its purity. 

The formation of emboli by clots or fibrine, and the intro- 
duction of air, have been spoken of as dangers inherent to the 
operation. These certainly existed when the apparatus was im- 
perfect. But improved instruments have done away with all 
risks, and, of late years, among a number of operations which 
have been performed, we have never heard any mention of em- 
boli or infarcts. It has happened that transfusion has not always 



TRANSFUSION OF BLOOD. 231 

succeeded in saving life. This has not been through any fault 
of the operation, but owing to the condition of the patient. 

Phlebitis and purulent infection have also been spoken of. 
These are possible; but phlebitis shows itself chiefly when a 
ligature has been applied too tightly ; if, on the contrary, the 
vein is held by fingers that know better how to measure pres- 
sure, there will be none of those rude attritions of the inner 
membrane of the vein, which eventually develop phlebitis, or 
give rise to the formation of a thombus. 

As regards pyemia and purulent infection, one might as well 
say we should, on their account, never practice blood-letting. 
We can, besides, always place ourselves on the safe side by 
removing the subject upon whom the transfusion is to be prac- 
ticed, into pure air, and placing him under such conditions of 
ventilation that purulent infection need no longer be feared. In 
conclusion, the operation is at present easy, exempt, we may say, 
from any objections ; and I shall now tell you what results may 
be expected from it. 

When a considerable quantity of more or less generous blood 
is first injected into a subject who is excessively pale and labor- 
ing under the effects of deep anaemia arising from hemorrhage, 
the face is seen to revive, the eye brightens, and the pulse, if 
very weak, picks up and acquires some volume ; if it was quick, 
it becomes more moderate, even calorification is somewhat repro- 
duced, and warmth extends to the extremities. These are the first 
effects ; there are others which are consecutive. 

There is an awakening of all the leading functions, as of 
respiration and nutrition, and this awakening bears no propor- 
tion to the quantity of nutrient materials, of globules, which is 
introduced. In a majority of cases it would seem this spurring 
is enough to arouse an organism apparently very seriously 
impaired. We shall notice a marked improvement in the mus- 
cular forces, the voice returns, the nervous functions resume 
action, the patient recovers sensation, the intellect, which was 
obscured, revives, so do the special senses — there is a general 
revival, which is gradual, or at times somewhat speedy. Appetite 



232 PRINCIPLES AND METHODS OF THERAPEUTICS. 

returns, so do the digestive faculties and sleep, which had been 
replaced by narcosis. If the patient has been subject to nervous 
phenomena, such as slight muscular spasms or convulsions — for 
you know that when the blood is greatly diminished, convul- 
sions take place resembling those in epilepsy or a rush of blood 
to the nervous centres — those phenomena cease. It would not 
avail as much if we only had these results, and if there did not 
remain a deep and durable re-animation enabling the organism to 
recruit itself. This also takes place providing the cause induc- 
ing anaemia is not a persisting one, and on condition that you are 
not in the presence of a necessarily fatal illness. If you are 
dealing with one of those organisms which, for some reason, can- 
not be re-animated, but which you galvanize, (this is the best ex- 
pression), by means of transfusion, you will find that after a time, 
either a day or forty-eight hours, the organism again sinks, all 
the functions become languid and lapse into their previous con- 
dition, and you find that the increased proportion of globules, 
of which you had determined the number, has also decreased. 

I witnessed a case in which the operation was performed by 
Dr. Brouardel, at Beaujon. Before the operation there were 
3,200,000 red globules; 150 grammes of blood were injected 
and the number increased to 3,500,000. At the end of thirty 
hours the number of globules fell back to the first figures ; the 
patient died, and this showed us that with his own powers he was 
unable to make globules. This suggests to you a way of ascer- 
taining the exact condition of your patient. 

The question has been asked whether repeated transfusions 
cannot keep up a sort of artificial life, and thus finally permit a 
return to health. It would seem not ; on animals the experi- 
ment has given no good results, and it has hardly been tried on 
man. 

A number of dogs have been taken and deprived of solid food, 
but they were given all the water they required. To a portion 
of them repeated transfusions of blood were made. The first 
lived twenty-three days, the latter died at the end of twenty- 
eight, although they were continually supplied with considerable 



TRANSFUSION OF BLOOD. 233 

quantities of blood. This shows that a supply of blood and 
globules is not alone sufficient to keep up life, but that the 
digestive organs must be called into action, they must receive 
food, and this food must be assimilated and perform all the 
functions required of it by the ecouomy. 

I shall now speak of indications and counter-indications, and 
I ask leave to divide transfusion into several categories. We 
first have preventive transfusion, intended to prevent accidents 
arising from extreme anaemia ; then repressive transfusion, whose 
purpose is to remedy the various evils caused by this anaemia. 
This last should be divided into palliative transfusion, that is, by 
the use of defibrinated blood, and really curative transfusion, 
which is practiced with the blood in its natural state. 

Preventive transfusion. For example, an individual meets 
with some terrible accident ; he is picked up weltering in his 
own blood, he revives, and his recovery depends upon an opera- 
tion entailing a further loss of blood. Evidently a surgeon 
would hesitate at such an operation unless he had the means of 
recruiting that organism so entirely depleted of blood. If, by 
the aid of a transfusion made prior to the operation, he is able 
to supply the patient with perhaps a greater quantity of blood 
than he is likely yet to lose, the operation will thus become pos- 
sible and very useful. 

Let us now consider repressive transfusions. 

We first have palliative transfusion, intended for a momentary 
revival of the organism. This can always be practiced, for there 
is always advantage in recruiting a patient's strength, and Brown- 
Sequard has gone so far as to say that these transfusions are ad- 
visable even at death's door. If he only intended thereby to 
postpone the fatal issue for a few hours, the operation is hardly 
desirable, but perhaps he thought of possible errors in diagnosis. 

Anyhow, without going so far, I will say that palliative trans- 
fusion, in a great many circumstances, may be useful and may be 
recommended. 

Curative transfusion. This presents positive indications and 
counter- indications. Nothing can be expected from transfusion 



234 PRINCIPLES AND METHODS OF THERAPEUTICS. 

when anaemia is caused by a cancerous cachexy or if it is clue to 
leucaemia, or to hemorraphylia. (You will notice, I do not say 
hemophilia, and that I use the y.) These diseases cannot be 
fought in this way. 

If you have to contend against poisonings caused by a deep 
organic lesion, or by a number of organic lesions, as is the case 
in uraemia, in which the kidneys have suffered degeneration, no 
benefit will attend transfusions of blood exempt from urea, no 
matter how often these transfusions are repeated. You will meet 
with no better success in septic diseases, because the poison is 
being continually renewed. As to old age, that is an ill from 
which there has been no recovery, since the waters of the fountain 
of youth were dried up. It is said an old dog was made 
young by transfusion. I am afraid, however, this was drawn 
from the imagination. I say the same of a number of patholo- 
gical conditions which have been considered amenable to this 
operation. Denys reports having injected the blood of a calf 
into a raving maniac, and that he had been improved. It has 
since been suggested that the disposition of persons could be 
modified, especially of those under pathological conditions, if the 
blood of young and mild-tempered persons was introduced in 
their veins. This, of course, does not deserve attention. But 
real curative transfusion can, on an emergency, be of service in 
troublesome conditions, such as essentially spontaneous anaemias. 
In chlorosis, when very strongly-marked anaemic phenomena 
are associated with that serious condition, there is no reason why 
transfusion should not be practiced. There are chlorotics who 
are in such a state of globular depletion that they can hardly 
walk a single step without being quite out of breath. It is evi- 
dent that if at this period of their ailment generous blood is in- 
jected into them, they will be greatly improved. Purpura and 
scurvy would also warrant injections. Albuminous and sacchar- 
ine diatheses, accompanied by very marked anaemia, may be 
counteracted by this method. 

Constrictions of the oesophagus and certain more or less serious 
affections of the stomach, which form a considerable obstacle to 



TRANSFUSIONS OF BLOOD. 235 

alimentation and consequently also to nutrition, admit even more 
of the introduction of blood taken from a healthy and vigorous 
subject than of the introduction of peptones into the cellular tis- 
sue. But there are positive indications for it in certain cases of 
serious syncope, with subjects who have lost a moderate quan- 
tity of blood, but who are enervated by a moral shock, and 
present the semblance of apparent death, cases allied to those 
which Dupuytren called nervous blood-lettings. In those cases, 
as in those of lethargy, blood might be injected with advan- 
tage. Also in certain asphyxias and intoxications, in which 
death is imminent ; when, for example, the globules have become 
impregnated with oxide of carbon, if it is possible to withdraw 
a portion of that blood and replace it by another which is pure, 
and capable of keeping up respiration and the other important 
functions, you will in this way save your patient. 

It is not probable that for some time to come, the foregoing 
advice I have given will be acted upon. An ordinary case for 
transfusion is inanition, where subjects have been deprived of 
food for a long time. Such an occasion would be an excellent 
one for injecting blood. Further, in certain exhaustions, such 
as those which follow prolonged suckling or losses of blood of 
all kinds, you may still momentarily revive the subject and 
prevent a continuance of the exhaustion. It is the same in 
cases of incoercible vomiting ; and especially in very abundant 
hemorrhages following an accident, or else that physiological 
traumatism which follows the puerperal state. It is above all 
among women after labor, when nothing has been able to put a 
stop to these hemorrhages of one, two, and sometimes more kilo- 
grammes, that transfusion becomes absolutely necessary, and that 
dependence must no longer be placed on the natural efforts. 
Among ninety-three transfusions practiced in cases of this kind, 
no less than sixty have resulted in the cure of women who were 
so thoroughly exhausted that they were in a dying state. This 
is undoubtedly a good result. 

Unfortunately there are but few indications by which we can 
judge when there is a necessity for transfusion. Profound col- 



236 PEINCIPLES AND METHODS OF THERAPEUTICS. 

lapse, torpor, and weak pulse have been mentioned as signs, but 
these are very vague. With animals the case is different. We 
can take precautions, and, guided by the use of the scales, it is 
easy to establish the following rule : when an animal has lost by 
hemorrhage, according to some, an eighteenth, according to 
Milne-Edwards, a twentieth of its weight, it is then time to in- 
terfere. But if you reflect what the eighteenth part of an ani- 
mal's original weight represents, with regard to the total quan- 
tity of blood, you will find that, admitting 5 kilogrammes as the 
average weight of blood in a man weighing 60 kilogrammes, he 
will have lost three-fifths of the total mass of his blood, or else 
four-fifths, if we admit the basis of a twentieth. Four-fifths of 
the blood is enormous. There would then only remain a single 
kilogramme of blood in the economy. This is about the same 
estimate that can be reached by other considerations which I shall 
indicate. But, unfortunately, we can have no knowledge of a 
woman's weight prior to her losses, hence we can form no esti- 
mate of the quantity of blood lost, especially as it is scattered all 
around and through the linen which it soaks. 

There is a process by which the retrospective diagnosis of the 
situation may be established. This is as follows : In the opera- 
tion performed by Dr. Brouardel, (I select that case because the 
globules were counted,) he injected 150 grammes of blood, rep- 
resenting 19 grammes of globules. If we rely upon the known 
composition of blood, this blood was enough to make an increase 
of an eleventh in the former proportion of globules, since 
3,200,000 were raised to 3,500,000. There were, therefore, 
190 grammes of globules in all, since 19 grammes represented 
an eleventh. Now if blood is in the ratio of 127 or 130 
grammes of globules to the 1000, we find that there must only 
have been 1.500 kilogrammes of blood in the patient. 

But allowance should be made for the fact that the globules 
must have been diluted in a large quantity of serum, in the ratio 
indicated between 3,200,000 and the average figure of 5,000,000. 
Therefore there was about five-twelfths of water in the patient's 
blood, that is to say, that to the 1.500 kilogrammes which we 



TEANSFUSIONS OF BLOOD. 237 

finl by calculation, we have to add five-twelfths — that is, 625 
grammes — which gives us a total of 2.125 kilogrammes. There- 
fore this patient, whose condition was so serious that transfusion 
was deemed necessary, had but two-fifths of the normal quantity 
of blood left in him. 

Thus, by the aid of a calculation, I have reached the same nu- 
merical result as experimenters have, who make tlmr observa- 
tions on animals. From this it follows that there is indication 
for practicing transfusion whenever the patient has lost three- 
fifths of the total amount of his blood. Only, as I remarked, 
it is a pity that you cannot tell, before practicing transfusion, 
what is the quantity of blood remaining in circulation. 

I am now through with the history of transfusion. It may 
have appeared tedious to you, but the subject is a very interest- 
ing one and daily growing in importance. Much attention is 
being bestowed upon it, and if we take the total number of 
transfusions which have been made, including even those with 
defibrinated blood, however incapable they were of realizing the 
hopes placed upon them, since they could but temporarily revive 
the organism, we shall find that out of 270 cases of transfusion 
there have been at least 150 successes. 

I therefore sum up with the conclusion that when a method 
is easily applied, is exempt from real dangers and gives such 
results, when death is almost imminent, it should be recom- 
mended, and full credit is to be given to those who are endeavor- 
ing to extend its use. 



238 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XXI. 

Injections into the Blood. — Transformations Un- 
dergone by Medicaments. 

Medicinal infusions into the blood. — Intravenous injections. 
Transformations Undergone by Medicaments in the Organism : 
Immediate Changes — Nitrate of silver. 
Changes in the Primce Vice — Temperature.— Cold drinks.— Negative functions 

of the mouth. — Active functions of the stomach. 
Modifications in the Intestine — Functions of fatty bodies, and of albuminous 

matters. — Gas. 



Gentlemen : 

Let me now briefly notice medicinal infusion — that is, the 
introduction of medicinal substances into the veins. This opera- 
tion is not as ancient as the transfusion of blood, although it is 
more simple and apparently more natural. As I stated, both it 
and transfusion were proffered to the Bishop of Exeter. It 
would seem Fabricius likewise practiced the infusion of medi- 
cines into the veins. But it is really only in the early part of 
this century, about 1802 or 1803, that Doctor Scheel revived 
the practice. Since then it has been often repeated, but never 
under favorable conditions. The fact is, as I shall hereafter 
point out to you, there seems to be no occasion for this operation, 
which we can very readily replace by other methods. 

Tepid water has been injected into tetanic patients. The great 
physiologist, Magendie, succeeded by this means in stopping 
the spasms, but this did not prevent the patient from dying at 
the end of two days. Bennett repeated the same experiment 
and met with like results — an immediate discontinuance of tonic 
convulsions, followed by a fatal termination within a given time. 



INJECTIONS INTO THE BLOOD. 239 

It was especially during the prevalence of cholera epidemics 
that the use of these intravenous injections was in favor. In 
this disease, death seemed to be brought on by the subtraction 
of a large quantity of serosity from the blood, since nothing but 
pure serosity is poured into the intestine — so much so that the 
pulse becomes imperceptible. It was, therefore, thought that 
some benefit could be derived by injecting into the veins water 
containing the salts belonging to blood serum. As the belief 
prevailed that sulphate of soda, when injected into the veins, was 
a purgative of considerable energy its u c e was avoided, and in its 
place more or less diluted solutions of chloride of sodium and bi- 
carbonate of soda were used. The immediate results appeared 
very favorable. I have even seen persons who seemed revived, 
in whom circulation started a- fresh, but notwithstanding this 
they died, because this method availed but against one of the 
toxical symptoms and not against the persistent cause which de- 
termined the fatal results. 

Natural serum has been injected without giving any better 
results than the solution of carbonate of soda. Nor have a num- 
ber of other medicaments when injected. Acetic acid has been 
suggested — no one knows why ; but we could understand the 
use of laudanum, because it would contribute to the recruiting 
of strength. Solutions of strychnine have also been tried, be- 
cause it seemed necessary to revive and galvanize the medullary 
nervous system. In company with Dr. Duchaussoy, I once 
made an intravenous injection of 20 centigrammes of sulphate of 
quinine and met with an absolute failure. Yet sulphate of 
quinine seemed well indicated as a means of action against a 
disease which has been compared to and behaves like a pernicious 
intermittent fever; besides, it could at the same time act as an 
antiseptic and an antizymotic, and thus answer a double object. 
But it had not the least effect in spite of all our anticipations. 

Emetics and purgatives have also, at various times, been intro- 
duced into the veins, under the belief that their effects would be 
more prompt. As I before remarked, this was a mistake ; the 
results could only be indifferent, since those substances must cir- 



240 PRINCIPLES AND METHODS OF THERAPEUTICS. 

culate and be eliminated before they can act on the intestinal 
muscular membrane and on the mucous membrane itself. 

Finally, a German physician injected castor oil into his own 
veins. A dose of 15 grammes has been mentioned. I have not 
read this figure in the text, so I cannot guarantee the dose, but I 
am inclined to believe it was 15 grains. However that may be, 
the operation appears authentic. The experimenter felt some- 
what unwell, experienced a taste of castor oil in the mouth, had 
some intestinal troubles and a desire to throw up, but nothing in 
the way of an alvine evacuation. Therefore, with regard to a 
cathartic effect, the result was void. 

As to neutral salts, laboratory experiments have proven that 
they are constipating and do not occasion diarrhceal stools ; con- 
sequently, all such experiments, good for a time when science was 
undeveloped, should not be repeated now. 

Although a great many active medicaments have been discov- 
ered, they have not been applied to intravenous infusions. Even 
morphine and strychnine, which are so generally used, have not 
been injected into human veins by this method ; but with regard 
to experiments upon animals, we may say that almost every 
active substance has been tried. The reason of it is that while 
chemistry was placing at our disposal a number of active prin- 
ciples, there were other methods rendering their passage into the 
economy so easy that infusion was not thought of. It is only 
accidentally that physicians have been called upon to witness the 
effects of active substances when introduced into the veins, prin- 
cipally, when in a hypodermic injection the needle penetrated 
into a small vessel. This accident, as I have already men- 
tioned, may be followed by the most serious effects. 

Several cases of death from atropine took place in Paris, in 
1867-68. In a number of these the quantity introduced under 
the skin was not large, and the patients had previously had 
similar doses, without accident. I have no doubt that in those 
cases the substance encountered some venous branch into which 
it was introduced suddenly. 

Of late years a distinguished surgeon, Mr. Ore, of- Bordeaux, 



INJECTIONS INTO THE BLOOD. 241 

has made himself the champion of intravenous injections of 
chloral, which he proposes substituting for other anaesthetic 
substances, for the purpose of producing anaesthesia ; lie reported 
a number of apparently favorable cases, and several surgeons, 
principally foreigners, have followed his method. I consider it 
injurious. In several cases this plan has not caused any serious 
accidents ; there have been no deaths ; but death has taken place 
in a number of experiments. One might have though that the 
animals that perished were under different conditions from man, 
and that the same precautions had not been taken; but Mr. Ore 
himself has had one fatal case.l Several others have happened, 
due to injections in cases of tetanus ; I do not pretend to say 
that the patients would not have died within a few days, but 
here they expired under the influence of an artificial poison. 
Those results are easily understood. When chloral is introduced 
into the veins the dose must be massive, and may be greater 
than can be tolerated by the organism under treatment ; with 
chloroform we can always set aside the terrible agent we are ap- 
plying, but here there is no way of withdrawing the active sub- 
stance, the proper dose may be exceeded, and produce such deep 
narcosis that the revival of consciousness and the organic facul- 
ties may no longer be possible. 

Another very serious disadvantage is the coagulation of blood 
in the veins. Chloral is a coagulent which can be used for tan- 
ning and preserving tissues. Mr. Personne lately showed us at 
the Academy a brain preserved in chloral for a very long time, 
and we know that chloral coagulates blood as powerfully as 
phenic acid does. Therefore, when you introduce a solution of 
chloral, it must be a massive dose, because if over-diluted it 
would produce a commotion of the heart. Thus you risk caus- 
ing a coagulation of the blood, and giving rise to emboli, to 
infarcts, and to a suspension of life in some of the essential 
organs. 

In conclusion, this method of intravenous injections has never 

s x Ore\ " Chloral and Intravenous Medication." "Studies on Experimental 

Physiology; Application' to Therapeutics, and to Toxicology." Paris. 1877. 



242 PRINCIPLES AND METHODS OF THERPEUTICS. 

been able to gain a foothold in French practice. It exists in 
other countries where they are bolder, but here it has been ener- 
getically rejected by the Academy of Medicine, and I fully en- 
dorse that course. 

I have now to consider the alterations undergone by medica- 
ments. This is a very long chapter in general therapeutics, and 
one that deserves careful perusal in all its details. I shall chiefly 
consider the modifications suffered by medicaments when they 
are applied upon surfaces, or introduced into the interstices of 
the cellular tissue, and shall follow these medicaments in their 
course through the circulation, and in the secretions, wherever 
they may be attracted prior to their final issue from the organ- 
ism. 

There is, however, a chapter in medicinal transformation which 
here deserves mention. It is that concerned with the changes 
brought about in medicaments by the preparations in which they 
are administered to patients. 

Pills of nitrate of silver are prescribed under the belief that 
they produce a catalytic effect on the digestive membrane ; that 
they act as a stringent, determine favorable modifications, and 
bring on a cure. But the fact is, nitrate of silver is never intro- 
duced, or if it is, then the quantity is so trifling that it is insig- 
nificant. When powdered nitrate of silver is mixed with bread 
crumbs, in a very few moments the silver is reduced, and chlor- 
ide or albuminate of silver is formed. More than seven-eighths 
of the nitrate of silver is thus decomposed into metallic silver. 
After a few hours' standing, the preparation contains no more 
nitrate. This proves that theories should not be constructed 
upon facts that are not fully established, and that often a sub- 
stance is supposed to be administered when it is not. 

Let us now consider the mutations which medicaments under- 
go when in the organism. These changes are of a physico- 
chemical nature. We shall study them in the prima? via?, in 
contact with the surfaces upon which remedies are applied, in 
the blood, in the secreting organs, in the recesses of the tissues, 



ALTERATIONS OF MEDICAMENTS. 243 

and finally in the natural reservoirs in which they remain for a 
given time after having been eliminated. 

Among the physical changes produced in the primce vice, 
those of temperature are interesting, because they are very im- 
portant. 

When a cold drink is introduced, its temperature is elevated by 
subtracting heat from the organs with which it comes in contact ; 
thus a local sedation is produced which gradually extends itself 
through the whole system, revealing itself in proportion to the 
reduction in temperature. In febrile conditions cold drinks are 
the most sedative agents, hence they have always formed an ele- 
ment in an antiphlogistic regimen. 

Let us now examine the chemical changes undergone by active 
substances in the primce vice. As I remarked, these changes are 
of vast importance, and they exert a great influence on the ulter- 
ior results and the form and activity of the pathogenetic phe- 
nomena which medicaments determine. 

You must bear in mind that throughout the organism there 
are everywhere substances possessed of comparative activity, and 
capable of modifying medicamental agents. Alkalies, acids and 
alkaline chlorides are everywhere to be met with. You will 
presently see that these different substances exert a very marked 
and often a decisive influence on the direction in which medica- 
mental mutation takes place. 

The mouth calls for no special remarks — food only passes 
through it on its way to the stomach. 

The stomach contains substances which in their normal state 
are of very great activity, according to some physiologists ; these 
are lactic, chlorhydric, or phosphoric acids. Normal ferments 
are likewise present, as pepsin and its two modifications, if you 
will concede them — that is, the coagulating and dissolving fer- 
ments. Besides these, there are accidental ferments borrowed 
from the atmosphere, or developed under the influence of 
changes produced in the organ itself, at the expense of the ali- 
mentary substances. And you will also find it to contain atmos- 
pheric gases, as well as water. 



244 PRINCIPLES AND METHODS OF THERAPEUTICS. 

When organic substances are introduced into the stomach, 
they undergo all these influences, and if there is considerable 
gastric activity, as for example, during the digestive process, 
they will experience such important changes that it may happen 
their effects will be entirely neutralized. You introduce aconi- 
tine but obtain no results, not even with high doses. Atropine 
and morphine are subjected to the same destruction. Even 
quinine and the proximate alkaloids which are so persistent, ara 
not able to resist being modified, so that at meal-time consider- 
able quantities can be taken without obtaining the desired results. 

You should always be on your guard against this species of 
stomachic digestion, which is a cause of reduced activity in medi- 
camental substances. The only remedies which should be intro- 
duced at meal-time are those requiring previous dissolution, 
those acting in the same way as histogenics and metallic sub- 
stances, from which the metal element is alone desired, such as 
iron, manganese and arsenic. For all the others another hour 
should be selected. 

The acids in the stomach likewise exert great influence. They 
increase the solubility of salts, for, as you are aware, the majority 
of salts are rendered more soluble by an excess of acid. Bases 
are also salified by those acids. Thus the oxides of iron, of zinc 
and of calcium are salified and dissolved by the acids contained 
in the stomach. With regard to iron, this is of great importance, 
because we very frequently introduce oxides of iron, relying upon 
the acids in the stomach to effect their solution and procure their 
passage into the circulation. The acids in the stomach also de- 
compose such carbonates as those of lime, soda, potash, magnesia 
and iron-rust. Consider how important are these facts. When 
you desire to diminish the gases and acids of the stomach, you 
must not prescribe carbonate of magnesia, but calcined mag- 
nesia. The carbonate would only have a tendency to increase 
the disorder by producing carbonic acid gas. 

Finally, metals themselves, w T hen free and introduced in an 
uncombined state, are dissolved by the acids in the stomach. 
However, this solution is due to a double reaction. These 



ALTERATIONS OF MEDICAMENTS. 245 

metals are not directly soluble in the acids of the stomach, unless 
chlorhydric acid is present, and in sufficient quantities. They 
have first to be oxidized by the oxygen contained in the stomach. 
These oxides then combine either with the phosphoric or the 
lactic acids. Hydrogen is liberated and remains free, unless 
other elements are present ready to combine with it. When that 
is the case, if you administer iron to a chlorotic patient, she will 
have inodorous eructations — (pure hydrogen.) On the contrary, 
if the stomach contains albuminoid or nitrogenized alimentary 
substances in which sulphur enters, the eructations (formed of 
sulphuretted hydrogen, the latter having combined with the sul- 
phur,) will be malodorous and have the smell of rotten eggs. 
You understand how important it is to fully comprehend those 
reactions, so as to know the disadvantages which follow the ad- 
ministration of certain medicaments, that you may explain them 
to the patients and avoid them. 

In the stomach oxygen is also found. It has the effect of 
raising substances from a low to a higher degree of oxidation ; 
that is what happens with sulphate or carbonate of protoxide of 
iron. It is important you should know that sulphate of iron 
can be of no possible service in globular recuperation. It might 
be continually and for years transfused into the veins of an 
anaemic patient without producing a single additional globule. 
Yet when sulphate of protoxide of iron is introduced into the 
stomach, the globules are increased. This is due to the process 
I have explained. It is converted into a sulphate of the per- 
oxide of iron, which becomes basic. There is an ulterior oxida- 
tion, and a change to a higher condition. 

This free oxygen oxidizes all substances introduced either at a 
low state of oxidation or absolutely free. Thus if sulphurous 
acid is introduced, it has been suggested that it will be changed 
into sulphuric acid. When phosphorus is introduced into the 
stomach, it passes to a higher degree of oxidation, and also un- 
dergoes other mutations due to the presence of water. Phos- 
phorus decomposes water, and forms, on the one hand, phosphorous 



246 PRINCIPLES AND METHODS OF THERAPEUTICS. 

acid, and on the other, phosphuretted hydrogen. Therefore, 
this is another kind of modification. 

Let us now consider the mutations which medicaments under- 
go in the intestine. No doubt, we shall again meet with a num- 
ber of those which take place in the upper portions of the 
digestive organs, but besides these there are others which mani- 
fest themselves. 

If the stomachic liquid is acid, the intestinal is always alka- 
line, except that of the caecum, which is said to be acid. How- 
ever that may be, the alkalinity of the digestive duct is a general 
rule ; it is due to the presence of bicarbonate of soda ; when the 
acid substances from the stomach penetrate into the intestine, 
they encounter this alkali, which partly saturates them and 
liberates the carbonic acid with which it was combined. If 
substances acting the part of a base present themselves, combina- 
tions are formed, and by their aid these substances which of 
themselves would have been insoluble, are made to pass into the 
circulation, and produce their effects. 

When colophony is introduced into the digestive duct, it is 
softened in the stomach, but in the intestine it can be dissolved, 
because there it becomes saponified, the same as all other 
terebinth ines. They then form compounds which are called 
resinateSj that is, in which the acid is represented by the resin. 
These substances then become soluble, pass into the circulation, 
and are carried, some towards the respiratory organs, others in the 
urinary organs, there to determine all the effects you know. 

Substances which are only soluble in an excess of acid, are 
naturally precipitated when they enter the intestine and meet a 
liquid charged with alkali. 

There is also a group of substances acting the part of solvents, 
and which, as such, have not been long known, but they are im- 
portant, and deserve passing notice. I have reference to fatty 
bodies. They exist everywhere in the intestine, and are the 
solvents of such substances as sulphur, and especially phosphor- 
us. Therefore oil and every other fatty substance should be 
carefully avoided in cases of poisoning by means of phosphorus. 



ALTERATIONS OF MEDICAMENTS. 247 

Let us now consider the chlorides, which are everywhere dis- 
tributed, bat chiefly in the mucus. This you can verify by 
dropping nitrate of silver on mucus, when a white precipitate of 
chloride of silver will immediately be formed. The chlorides of 
the first groups have the singular faculty of combining with 
those of the last, so as to form real combinations in which the 
alkaline chloride acts the part of a base, and the other that of an 
acid. Chlorhydrates of chlorides are thus formed, having the 
property of being very soluble, while the others are very hard 
to dissolve. Thus, for example, take calomel, which is insoluble, 
and chloride of silver, which is but slightly so, associate them 
with a solution of chloride of sodium, and by the fact of this 
combination they will become soluble. Perhaps an exchange of 
base takes place. Mialhe believed that under these conditions 
the protochloride of mercury takes up part of the chlorhydric 
acid, and becomes a bichloride. But it may be, as has been be- 
lieved, and as I think, that solubility results from the formation 
of a new salt. I have always opposed Mialhe's opinion, even in 
1847, during Trousseau's time; I have made some mention of 
it in The Art of Drawing up a Formula, which is annexed to 
Trousseau's and Pidoux* treatise. 

Calomel, for another reason, is not converted into bichlo- 
ride, otherwise all we should have to do would be to give 
calomel in order to obtain mercurial salivation, which is readily 
produced by the bichloride. This clinical fact alone warrants 
the declaration that this is not the process by which calomel 
penetrates into the economy. We shall presently find direct de- 
monstration in support of this. 

We are thus brought to consider the importance of the albu- 
minoid substances which are found in the intestine, and through- 
out the whole of the digestive duct. But their real mission is 
confined to the intestine, where they facilitate the penetration of 
different substances. They are not only emulsive agents, but 
perform the office of real solvents. It was formerly believed 
that those substances acted the part of gum arable j that they 
divided insoluble substances, and by means of this division facil- 



248 PRINCIPLES AND METHODS OF THERAPEUTICS. 

itated their introduction into the circulatory organs. That is 
not what takes place. 

Albuminoid substances, such as albumen, the different kinds 
of mucus, and legumin, are real solvents for a great number of 
metallic substances, which they dissolve, because they combine 
with them. Real albuminates . and leguminates are formed. 
Gluten might also be used, because it is an albuminoid substance. 
It is by means of the mucus that calomel is dissolved. This 
has been proven. Mr. Personne has made experiments in 
which he has dissolved calomel in mucilaginous substances. 

It has long been known to chemists that albuminoid substances 
behave in a very peculiar manner when in contact with salts, 
such as those of zinc, copper, lead, silver, gold and platinum. 
When albumen is added to a solution of sulphate of copper a 
precipitate is formed ; if more is added the precipitate re-dis- 
solves, and it may be again reformed if still more is added. This 
same fact occurs with a number of other substances. I have had 
occasion to notice it with perchloride of iron, although this is a 
powerful coagulating agent. 

These phenomena show themselves in a very marked degree, 
especially in the case of nitrate of silver, and they have been 
applied to good practical use in injections of that substance. 
When nitrate of silver is dissolved in albuminous water, this 
solution comes in contact with the intestine, without producing 
any strong chemical action, thereby avoiding the painful effects 
attending this action. The metallic salt gradually separates 
from its solution and acts upon the mucous membrane by modi- 
fying, in a very useful manner, its ulcerations. Delioux de 
Savignac, who took great interest in therapeutics, invented this 
process, and gave the following formula for an injection : Ni- 
trate of silver from 0.25 gr. to 0.50 gr. ; albuminous water 60 
gr. To this, 120 gr. of tepid water were added, when desired 
for use. This is the only true way of using nitrate of silver in 
injections, owing to its faculty of being dissolved by albumen. 

We can now understand how those albuminoid substances, 
which are found in such abundance in the digestive duct, are 



ALTERATIONS OF MEDICAMENTS. 249 

able to dissolve calomel which penetrates into the organism as an 
albuminate of protochloride of mercury, and behaves like calo- 
mel. This likewise applies to protoiodide of mercury, to sul- 
phur, phosphorus, and to all substances that are soluble in mucus 
and albuminoid bodies. 

The digestive duct also contains large quantities of gases — 
sulphurretted hydrogen, and, in some cases, sulphide of ammonia. 
Of course, there is no oxygen, otherwise the sulphuretted hydro- 
gen would be consumed. For a like reason, oxygen is never 
found in sulphuretted mineral waters. In some instances the in- 
testine also contains nitrogen. 

The sulphuretted hydrogen also causes changes in medica- 
mental forms, when metallic salts, having gone through the first 
part of the digestive duct, reach the duodenum, and that portion 
of the lesser intestine in which there already exist faecal matters. 
These saline substances may then be transformed into sulphides 
of iron, bismuth or zinc. This has its importance, because 
it is a way of neutralizing the effect of these active substances. 
Sulphides are very insoluble, and they pass through the digestive 
duct without causing any effects, since bodies only act when in a 
dissolved condition. But there is another important point. It 
is that the faeces reveal by their color when an excess of active 
principle has been introduced. 

It is generally believed that considerable doses of iron are re- 
quired to restore the globules and too much is almost always 
given. Thus, oxide of iron or reduced iron is always given, 
in doses of 0.50 gr. This is entirely too much. The same may 
be said of mineral waters when very strong, such as Spa, Orezza 
and Forges-les-Bains, which always leave an excess of iron, so 
that when a patient does not fully assimilate them, it is shown 
by the color of the stools. The physician, in such cases, reduces 
the dose of water to be taken. 

Another peculiarity to be noticed is, that in a number of cases 
these sulphides are apt to deceive, when there exists a possibility 
of intestinal hemorrhages. Blood becomes black when altered 
by acids or by sulphuretted hydrogen. When substances of that 



250 PRINCIPLES AND METHODS OF THERAPEUTICS. 

kind, producing a black sulphide, have been administered, it is 
sometimes difficult to tell whether a hemorrhage has taken place. 
Subnitrate of bismuth in diarrhoea blackens the faeces, which 
constitutes an objection to it when used in typhoid fever. For 
this reason I suggested giving oxide of zinc in place of the bis- 
muth. It is a good absorbent of acids and gases, and can there- 
fore render the same services. The oxide of zinc should, how- 
ever, be associated with bicarbonate of soda, so that the adds 
from the stomach may be more speedily absorbed. For here is 
another difficulty — when oxide of zinc absorbs lactic or chlorhydric 
acids in the stomach. Chloride of zinc is then formed, which is 
a salt possessed of highly irritating, nauseating and emetic quali- 
ties. To avoid this I give it in large doses, because the larger 
the dose the less does this phenomenon show itself. It is only 
the neutral lactate which is nauseating. If you have a basic 
chloride enveloped in a mass of inert substance, you will not 
encounter the same objections. But when giving oxide of zinc 
with bicarbonate of soda, the same results are obtained as with 
subnitrate of bismuth, without the inconvenience of having 
black stools. Consequently this does away with the difficulty 
of discovering whether there has been an intestinal hemorrhage 
in diseases in which such an occurrence is possible. 



ALBUMEN AND THE ALKALINE CHLORIDES. 251 



CHAPTER XXII. 
Albumen and the Alkaline Chlorides — Arsenic. 

Albumen and the alkaline chlorides ; role of Albumen in the economy: ab- 
sence of certain chemical phenomena in the human organism. 
Arsenic. 



Gentlemen : 

I have endeavored, in the concluding portion of the preceding 
lecture, to impress on your minds the importance of the albu- 
minoid principles ; I shall now demonstrate, or at least indicate 
to you, that albumen and the alkaline chlorides have the same 
dissolving action on medicaments, when introduced into the 
superficial or profound subcutaneous tissue, or when they are 
placed in contact with the denuded dermis. 

Under these conditions the same phenomena which we have 
observed in the alimentary canal, when albuminoid principles 
wore present, occur also when medicaments are placed in contact 
with the dermis denuded by a flying blister which has induced 
very little effusion ; so that substances not notably soluble, such 
as calomel, oxide of gold, aurum redactum, or even oxide of 
iron, may thus become soluble through contact with albuminoid 
matters and alkaline chlorides present in the different regions 
where they are thus applied. 

But it must be acknowledged that of all the parts of the body 
by which it is possible to introduce remedial agents, the stomach 
possesses the greatest power of absorption ; for instance, albumen 
can form a soluble combination with alum, but solely if in pres- 
ence of an acid; you can then very well understand that an albu- 
minate of alum, insoluble of itself, becomes soluble in the 
stomach, that organ always containing an acid — phosphoric acid, 
according to some observers, lactic or hydrochloric, as affirmed by 



252 PRINCIPLES AND METHODS OF THERAPEUTICS. 

others ; the stomach must then be considered the most favorable 
organ for the introduction into the system of substances requir- 
ing special conditions to become soluble. 

I have already demonstrated to you that albumen possesses the 
property of facilitating the dissolution of certain substances in- 
soluble under ordinary conditions ; but it possesses, also, another 
property, which might be expressed by saying that it acts as a 
suspending agent, hindering certain chemical phenomena which, 
without its presence, might occur ; a moment ago I demonstrated 
to you that it aided the absorption of active principles ; at present 
I will show you that this same albumen hinders these substances 
from undergoing modifications which, if it were not present, 
they would suffer. 

Take, for example, the reaction of sulphate of iron with car- 
bonate of soda ; by double decomposition, an insoluble salt, the 
carbonate of the sesquioxide of iron, is formed, and this reaction 
has been brought forward as offering a possible explanation of 
the manner the ferric salts are utilized in the reparation of the 
blood corpuscles ; for, it has been said, the sulphate of the per- 
oxide of iron coming in contact in the blood with bicarbonate 
of soda there present, a double reaction takes place, that the 
carbonate was freed, the carbonic acid escaped, and that the re- 
maining peroxide of iron, uniting with the globules, increased 
their redness ; but this supposition, besides not sufficiently ex- 
plaining the action of the ferric salts on the blood, is not even 
correct ; for when the experiment is made in the laboratory, with 
an albuminous solution of bicarbonate of soda, no precipitation 
takes place. 

Again, if to a solution containing silver, bromide of potash, 
and albumen, chloride of sodium is added, so as to form chloride 
of silver, you will not have any precipitation, the albumen 
present preventing its formation ; even in the first solution pre- 
cipitation might occur, but for the presence of albumen, which 
here again acts in opposing the realization of Berth ollet's laws. 

It may be objected that in such a solution there is no precipi- 
tate, because albumen acts as a dissolving agent, and though 



ALBUMEN AND THE ALKALINE CHLORIDES. 253 

chloride of silver is formed it is not precipitated ; but here is 
another case where this objection is not tenable : lactate of iron 
is introduced into the circulation by direct injection, or by ab- 
sorption ; the attempt is then made to demonstrate its presence 
in the serum of the blood by means of ferrocyanide of potas- 
sium ; some coloration should be produced, yet neither Prussian 
blue nor the French blue, which a protosalt of iron should give, 
is obtained ; the absence of blue tinge shows that no Prussian 
blue has been formed ; in other terms, that the new combination 
has not taken place ; yet if acetic acid is added the blue tinge 
appears ; the acid has simply modified the albuminoid principle, 
depriving it of its functions ; for we already know that albumen, 
according to its modifications, may hinder, or, on the contrary, 
aid in, the speedy formation of combinations. 

In photography, albuminoid plates are used, and without hin- 
dering the production of the reaction ; but the albumen is dry, 
and not being modified, acts in opposition to the realization of 
a certain number of chemical phenomena observed when the 
albumen is in solution in a test-tube or watch-glass. 

I have said that in the experiment mentioned above, if acetic 
acid is added the tinge of Prussian blue is obtained. Claude 
Bernard has taken advantage of this fact to demonstrate that the 
gastric juice is secreted solely in the superficial layers of the gas- 
tric mucous membrane, and not at the bottom of the glandular 
euls-de-sac. 

After introducing lactate of iron into the circulation, he 
painted the internal aspect of the stomach with yellow ferrocya- 
nide of potassium, and the blue tinge obtained was confined to 
the superficial layers of mucous membrane ; showing clearly that 
the acid necessary in the presence of albumen for the production 
of this reaction was present only in these superficial layers. 

These facts, as you see, are very curious, but may be consid- 
ered as following certain general rules. 

This action, suspending chemical phenomena which should 
occur, according to the laws of Berthollet (which laws have beeD 
more or less modified naturally since he first announced them), 



254 PRINCIPLES AND METHODS OF THERAPEUTICS. 

this action, I repeat, is observed in the human organism and in 
the circulation ; albumen will exercise its suspending properties 
on substances introduced into the blood and circulating in the 
serum of that fluid ; thus preventing the manifestation of a cer- 
tain number of chemical phenomena which would have occurred 
if it were not present. Take, for instance, this phenomenon, to 
which I have already alluded, of precipitation when a soluble 
body is introduced into the blood ; thus a quinine salt, though 
an alkaloid, coming in contact in that fluid with carbonate of 
soda, is precipitated ; as are also the salts formed by peroxide of 
iron. Now, if this precipitation really occurred, as .Mialhe be- 
lieved, what would happen? Why, just as long as these sub- 
stances capable of causing precipitation appeared in the blood, 
emboli would be formed, which, being arrested in the capillary 
vessels, would induce dangerous accidents ; and M. Mialhe con- 
sidered even that the febrile state was modified in this manner by 
quinine, that the emboli thus formed penetrated in small parti- 
cles into the capillary circulation, and thus acted in opposition to 
the phenomena of hsematosis, which are the primary cause of the 
febrile state! But I again repeat that if such emboli were 
formed accidents would result analogous to those observed when 
tobacco seed or lycopodium in powder is introduced into the 
vessels of an animal. But there is yet another fact which would 
not be observed if chemical phenomena were affected in the 
blood as in the laboratory ; the mineral acids introduced by the 
stomach to act on the blood, as when lemonade acidified with 
sulphuric or chlorhydric acids is given, the acid contained should 
combine with the soda of the blood to form sulphate or phos- 
phate of soda, and consequently an excess of acid would never 
appear in the urine ; and' yet, though I concede that there is 
great difficulty, I consider it possible to modify the alkalinity of 
the urine, a state observed to be the normal condition for mauy 
persons not over robust, or affected with catarrh of the respira- 
tory organs ; but it is difficult to render such urine acid, and 
large doses are required. 

Consequently, here are acids which pass in the free state 



ALBUMEN AND THE ALKALINE CHLORIDES. 255 

through the system to the kidney, and are excreted therefrom 
without change, which certainly would not happen if they came 
in contact with bicarbonate of soda in the free state, as in Vichy 
water, as phosphate of soda would be most certainly formed. 

Pereira, whose work on therapeutics is classic in England, 
affirms that when hypochlorite of soda, known in France as 
Javel water, is introduced into the stomach, the urines carefully 
collected contain either free chlorine or hypochlorous acid, and 
that they even possess bleaching properties. 

All these examples will serve to demonstrate to you that 
substances which, according to chemical laws, should combine 
with other substances existing in the blood, make the round of 
the circulation without being combined, and are found in the 
urine unchanged and capable of manifesting their peculiar pro- 
perties. 

But there are other facts equally interesting ; certain substances 
eminently oxidable can make the round of the circulation with- 
out suffering oxidation; demonstrating that while in the blood 
they have not undergone the chemical transformation which their 
nature would seem to require, they have not entered into combi- 
nation with the oxygen contained in the corpuscles of the blood, 
to pass to a higher state of oxidation ; take, for instance, pyro- 
gallic acid; there is no substance more void of oxygen, yet this 
acid has been introduced by Claude Bernard into the circulation, 
and has been found without alteration, and in the free state, in 
the urine of the animal. Here, again, we are obliged to recog- 
nize that combinations which, according to ordinary chemical 
laws, should occur, are impossible in the blood. Again, I will 
cite another instance, for these facts are many of them unknown, 
on account of their dissemination in many works ; chloride of 
barium, introduced in a soluble state into the stomach, penetrates 
into the blood, there meeting with sulphate of soda; it should be 
immediately transformed into sulphate of barium, which, under 
ordinary circumstances, is formed with such facility that the salts 
of baryta are never found in natural mineral water, for they 
always pass to the state of sulphates and are consequently de- 



256 PRINCIPLES AND METHODS OF THERAPEUTICS. 

posited in the earth; but this change, so facile as it is, does not 
occur in the human economy, and Woehler has shown that if 
chloride of barium is introduced, it is found unchanged in the 
secretions. 

There are other very interesting experiments, but from which 
I drew, perhaps, somewhat exaggerated conclusions when I men- 
tioned them, in 1867-68 ; these were the experiences of a chemist 
very well known through the observations he has made con- 
cerning the influence of iodide of potassium on the elimination 
from the system of metallic substances capable of inducing poison- 
ous effects. Melsens has shown that when iodide of potassium 
is administered, it causes the metals to reenter the circulation. 
This I have demonstrated myself in a case of poisoning by ar- 
senic; bat this chemist has also occupied himself with a very in- 
teresting question, to determine what influence might be capable 
of inducing in the human economy the effects obtained by means 
of the most powerful agents in the laboratory, such as mechanical 
force, or electricity, by which, as every one knows, certain bodies 
can be formed or destroyed. 

He took into consideration the question whether in the human 
organism the simple friction, the continual flow of the blood in 
the vessels, aided by a temperature of 37.5° C. in man, and of 
42° C. in birds, would not suffice to determine phenomena 
analogous to those obtained in the laboratory by the powerful 
means mentioned above ; he has arrived at affirmative conclu- 
sions on this question, and during his researches he has re- 
marked a curious fact : if iodide of potassium is introduced, it 
produces the effects proper to it, and no others ; the same state- 
ment is true of chlorate of potash, and either of these substances, 
given singly, are innocuous. Yet Melsens has demonstrated that 
these two substances, which do not react on each other in a test- 
tube, which remain as before, chlorate of potash and iodide of 
potassium, and which do not exchange the oxygen of the chloric 
acid with the iodine, except under certain determined conditions, 
when, for instance, the aid of electricity or mechanical force is 
brought into play ; he has shown that these two substances make 



ALBUMEN AND THE ALKALINE CHLORIDES. 257 

this exchange in the human economy when both are introduced 
together into the stomach, and that toxic accidents, often proving 
mortal, even for pretty large animals, are induced. The fact is 
of itself interesting, but here are the conclusions I drew there- 
from : I considered that if the two substances were introduced 
separately into the circulation, the one, for instance, by the 
stomach, the other by the rectum, that being absorbed apart from 
each other, and not coming in contact before arriving in the 
serum of the blood, they would not cause any fatal issue. I 
have not made the experiment, but I had considered it demon- 
strated by the following fact : large doses of chlorate of potash 
are given to a dog ; then, three or four days after, large doses of 
iodide of potassium, and no bad effect is perceived. From this 
last experiment I concluded that, this animal having remaining 
in his system a certain proportion of chlorate of potash, not 
being poisoned by large doses of iodide of potassium introduced 
immediately after, these substances, under such circumstances, 
came in contact in the blood, but that no noxious effects were 
induced, because in this fluid they could not undergo w the ex- 
change necessary to the formation of iodate of potash, which is 
the only noxious salt. 

But it might be objected that all the chlorate of potash had 
disappeared, or that, even when the iodide was given just im- 
mediately after the last dose of the chlorate, sufficient did not 
remain in the system for the formation of a notable quantity of 
the noxious iodate ; consequently, opinion on the subject must be 
reserved; but I am convinced that, conducting the experiment as 
I have mentioned, so that each salt should arrive separately in 
the blood, no toxic effects will be induced ; I will make the ex- 
periment, and in my course of lectures next year I will inform 
you if the results confirm the opinion I have expressed. 

I have, then, shown you that a certain number of chemical 
phenomena are wanting. I will now demonstrate that certain 
substances which have very marked physiological effects are 
deprived of such action when in circulation in the blood ; it will 



258 PRINCIPLES AND METHODS OF THERAPEUTICS. 

be the most striking demonstration of the influence of albumen 
on the state of substances introduced into the system. 

You all know what troublesome effects are induced by the 
application of a blister, too large, left too long in position, made 
up with more than usually powerful cantharides, or when ap- 
plied on a surface which absorbs too rapidly, as over a part where 
dry cups have been applied. 

You know that after a certain time painful symptoms supervene 
in the urinary organs, and that the active determination toward 
the kidneys and the bladder may cause the appearance of albu- 
men, of fibrin, or even of blood in the urine, and this last in 
quantity so considerable that there results a large mass of coag- 
ulum, filling the urinary reservoir, which induces dysuria, not 
from oliguria, but by presenting an obstacle to the passage of 
the urine ; I have seen individuals thus affected unable to urinate 
until the coagulum was dissolved ; you are all acquainted with 
these phenomena, but not many have reflected concerning the 
manner of their production. 

You observe an external surface absorbing a substance such as 
cantharidin ; the vessels which absorb this cantharidin and which 
are filled with it must, at a certain moment, experience the toxic 
influence of the drug; there should be phlebitis and even plastic 
phlebitis to explain the presence of albumen and blood in the 
urine ; very well ; in the absorbing system of the region where 
the blister is applied there is nothing abnormal, and no one has 
observed a lymphangitis or a phlebitis in the parts about the 
blistered surface, although such grave symptoms of kidney 
trouble have been induced by the application. 

How, then, can this be explained ? Can it be considered that 
the quantity of cantharidin present in the kidneys was large, 
while in the general circulation it was in very small proportion ? 
But no, there must have been as considerable a proportion in the 
vesicles which served to absorb it as in the kidney, consequently 
the facts cannot be thus explained ; the true reason is the pres- 
ence of albumen. 

Albumen being present, opposes the accomplishment of the 



ALBUMEN AND THE ALKALINE CHLORIDES. 259 

physiological effects usually produced by cantharidin ; but 
when, ou the contrary, the drug arrives in the kidneys — that is, 
when it is eliminated in a secretion which normally is exempt 
from albumen — it becomes free, and produces on the kidneys, on 
the parenchyma of these organs, and on the rest of the urinary 
apparatus, the effects which cantharides ordinarily determines on 
the skin, on the mucous membranes, and on all the surfaces with 
which it comes in contact. Can you not see in this instance the 
most striking demonstration of the influence of albumen on the 
working of chemical affinities, and on the combining properties 
of remedial or toxic substances introduced into the circulation ? 

It can, then, be said to be a general law that albumen modifies 
remedial agents in a certain manner ; that it aids in the dissolu- 
tion of a certain number, rendering their introduction into the 
economy more facile j but once introduced, this same albumen 
opposes in the blood the effects, whether chemical or physiolo- 
gical, which these remedies usually exercise on the organs with 
which they come in contact. 

That which I have just said may appear paradoxical, but the 
paradox of to-day may be a recognized truth to-morrow. Nev- 
ertheless, I do not go so far as to affirm that this influence of 
albumen is always absolutely or even generally exercised ; there 
are facts which seem to indicate that it does not hinder the pro- 
duction of certain chemical phenomena ; for instance, one of the 
exceptions that might be mentioned: I have said that urine nor- 
mally alkaline might be rendered acid by administering the 
mineral acids ; but I added, that to obtain this effect large doses 
were required, showing that a certain proportion must have com- 
bined with the bases with which they came in contact. 

Sulphide of potassium is in part decomposed when introduced 
into the blood j sulphuretted hydrogen is liberated by the car- 
bonic acid of the blood, and certain combinations take place, 
which may occur in the interior of the circulation, or, at least, 
during the passage of the drug through the system. There arc, 
also, combustible substances which may be burn-ad up and found 
in this state in the secretions. 



260 PRINCIPLES AND METHODS OF THERAPEUTICS. 

I have shown you that pyrogallic acid may be found un- 
changed in the urine, and yet we know also that a certain 
number of substances introduced into the circulation undergo 
oxidation through the presence of oxygen in the blood, or in the 
tissues. Alcohol, notwithstanding the fine experiments of M. 
Perrin, cannot be collected entirely unchanged in the urine; 
when very large quantities of alcohol are introduced, there is a 
large quantity which escapes without undergoing chemical change; 
but when the quantity ingested has not been too large, there is 
production of aldehyde, or alcohol deprived of hydrogen, and 
there is another part which passes to the state of acetone, acetic 
acid, carbonic acid, or of water. The essential oils are similarly 
affected if spirits of turpentine be introduced ; in the urine wil] 
be found a substance slightly oxidized, which gives to the urine 
the odor of violets, or a substance completely oxidized, a resin 
precipitable by nitric acid, will be collected ; consequently the 
essential oils are partly oxidized in their passage through the 
system, but I cannot affirm that this takes place in the blood. 

The alkaline salts are acted upon in the same manner. You 
are cognizant of Woehler's law ; that any organic acid originat- 
ing from the vegetable kingdom, when introduced into the sys- 
tem, enters into combination with potassa or soda, and is burned 
in the blood, and in the urine is found, not a citrate when citric 
acid is given, but a carbonate of soda. This offers an explana- 
tion of the modus operandi of the treatment of disease by fruit, 
grapes, cherries, or currants, which cause the urine to become 
alkaline, as do also the waters of Vichy and of. Vals. 

These facts have been reviewed and studied by Mialhe, who 
has rendered so many services to therapeutics and to physiology, 
and are now universally known. After the same manner, 
sulphide of potassium is excreted, in part, in the state of sulphate 
of potassa, that is, the sulphur has become sulphuric acid, and in 
this state has induced the formation of sulphate of potassa, which 
is thus excreted in the urine ; consequently you perceive that in 
a certain number of instances chemical phenomena are not 
impossible in the human economy. I have, however, shown 



ALBUMEN AND THE ALKALINE CHLORIDES. 261 

you that they are accomplished with difficulty, being rendered 
difficult by the presence of albuminoid principles surrounding 
the substances in the blood. 

I will continue the account of the chemical modifications pos- 
sible in the human organism; compounds are split up, and copu- 
lation between compounds takes place; as you are as well 
quainted w T ith chemistry as myself, it w T ill not be necessary for 
me to explain these terms. I have said that division of splitting 
up of compounds takes place; for instance, tannic acid splits up 
into gallic acid and glycol; it simply takes up water to add the 
necessary quantity of hydrogen and oxygen to that which it 
already contained. Again, copulation, or junction of different 
substances, is observed ; there are a certain number of vegetal) le 
acids which, introduced into the circulation, issue therefrom as 
acids containing nitrogen, which they did not before contain, 
but they have encountered in their passage those substances, ;he 
glycocolls, to which M. Wurtz has called attention; they combine, 
they copulate with them and give birth to new acids; this takes 
place, for instance, for benzoic acid, which becomes hippuric acid; 
this happens also for the much talked of salicylic acid. There 
are a certain number of essential oils which in the same manner 
copulate with glycocoll, to pass in the urine in the state of acids 
containing nitrogen. You see, we have quite a number of chem- 
ical phenomena which occur in the living organism, and are not 
hindered by the presence of albuminoid matters. There occur 
also phenomena of reduction which are very interesting. It is 
difficult to understand that substances which enter the blood in 
the combined state and at a superior degree of oxidation, can in 
the organism lose a part of the oxygen they contain, for the 
inverse is the general rule; for substances introduced into the 
human system most frequently absorb oxygen and aid by their 
combustion to produce animal heat or muscular force; there ex- 
ists, however, a certain number of substances which lose oxygen; 
thus, Woehler has long ago demonstrated that the red prussiate 
of potash, that is, the red cyanide of potash and iron (and which 
can be considered a cyanurate of potassium with peroxide of 



2G2 PRINCIPLES AND METHODS OF THERAPEUTICS. 

hydrogen), is reduced to the state of yellow cyanide of potassium 
and iron ; the demonstration of this fact is facile ; the salt is in- 
troduced into the system, and if it passed unchanged, after treating 
chemically the urines, the addition of sulphate of protoxide of 
iron should produce French blue; but nothing is obtained under 
these conditions, and if sulphate of peroxide of iron is added Prus- 
sian blue is obtained, demonstrating that the red cyanide has lost 
its oxygen and has become yellow cyanide. 

The same is true of the sulphate of peroxide of iron entering 
the system in this state; it is excreted as sulphate of the protoxide ; 
that is, if you give a good quantity to a dog it will be necessary 
to add red cyanide to the urine to obtain French blue. 

M. Rabuteau has encountered a similar experience : if seleniate 
of sodium is introduced, the selenic acid becomes selenious, a fact 
similar to that of M. Limousin, who observed that the protoxide 
of nitrogen could lose its oxygen and be transformed into nitro- 
gen, which for a certain time might serve to keep up respiration 
and consequently preserve life. 

But to these may be joined an entire series of hyperoxygenated 
substances, which Fourcroy had regarded as having considerable 
power, and whose number and importance he had, no doubt, 
exaggerated ; I think, however, he was right in admitting that a 
certain number of suroxidized substances could yield atoms of 
oxygen ; do I need to say that if he had known of the experiments 
of Claude Bernard, he would have considered them as aiding to 
prove his theory ? But in his time the composition of many sub- 
stances was not well known, or definitely settled. It has been 
remarked since, that chlorate of potash gave a scarlet tinge to the 
gums, as if a more active oxidation was being effected. Simpson, 
of Edinburgh, whose name is connected with the first application 
of chloroform to induce anaesthesia, employed chlorate of potash, 
convinced that it was a means of furnishing oxygen to the foetus, 
when it seemed to him, by the presence of certain signs, that its 
circulation or respiration needed stimulation. 

I have myself made analogous observations concerning the 
decomposition of chlorate of potash in the economy ; I have caused 



ALBUMEN AND THE ALKALINE CHLORIDES. 263 

the analysis to be made of the urine of subjects to whom I was 
about to administer it; this analysis demonstrated the presence of 
a certain proportion of chlorides; then I administered the 
chlorate of potash, and found an augmentation in the quantity 
of the chlorides; consequently showing you that a portion 
of the chlorate of potash was decomposed, and that the chloric 
acid had lost its oxygen; analogous facts have been observed 
concerning other substances, and permanganate of potash has 
been thus administered to modify haematosis when it appeared 
insufficient. For the same reason, Dr. Simpson administered it 
in diabetes, when, as you know, the combustion is slow and not 
sufficient. 

These facts are well established, yet they are still somewhat 
doubted by a certain number of physicians who have not suffici- 
ently considered the mutations which chemical bodies may un- 
dergo in the economy. But all the changes that may be consid- 
ered chemical take place elsewhere than in the blood ; the vessels 
are but irrigating canals or roads which bear to the different or- 
gans the substances which they will be called on to employ; in 
the blood itself just a mere exchange of substances takes place, 
as in a railroad station the different cars are separately loaded ; 
this metaphor will aid you in understanding what passes in the 
human system. Nevertheless, there are substances which really 
act while present in the blood, but they are gaseous or volatile 
bodies which act in the same manner as the air in respiration, 
directly on the blood corpuscles, and which accomplish their 
destiny, it might be said, in the blood itself; these substances I 
will cite to you ; they are hydrogen, carbonated (carburetted) hy- 
drogen, carbonic acid, and oxide of carbon, which spend their 
entire activity on the globules. 

The same is true of protoxide or binoxide of nitrogen — sub- 
stances which act in the circulation, as do, also, nitrous and hypo- 
nitrous acid ; and prussic acid, too, acts in the blood, as do the 
nitrites of amyl and of ethyl, and all the volatile and gaseous 
substances which induce anaesthesia ; as also the substances 
which nearly resemble them. These all induce phenomena 



264 PRINCIPLES AND METHODS OF THERAPEUTICS. 

which really pass into the blood, and no more striking proof of 
this truth is needed than their instantaneous and often fugacious 
action/ in the great proportion of cases. You are aware what 
passes when nitrite of anryl is inhaled ; it enters the lungs and 
acts with astonishing rapidity. This instantaneous action de- 
monstrates that it is in the blood that these substances have their 
action. This is what happens, also, in poisoning by sulphuretted 
hydrogen, which, in France, is called " le plomb" so named on 
account of the instantaneous nature of the accidents from it, the 
patients falling as if struck with a slung-shot (plomb meurtrier). 

The same is true of the anaesthetic agents. You all know with 
what rapidity and violence they act. They have a double action : 
at first on the blood, then on the tissues ; and this is true, also, 
of hyponitrous acid and binoxide of nitrogen ; these are gases 
which act directly and with excessive violence on the blood, but, 
unhappily, their action is not instantaneous. If in a certain 
number of cases their action is very rapid, it is because the oxide 
of carbon or the nitrite of amyl penetrate very rapidly into the 
globules. They do not quit the globules so easily, but contract 
with the haemoglobin combinations more or less stable, which 
cause the very dangerous nature of the accidents which ensue. 

I repeat it, the instantaneity of their effects shows that these 
substances act directly on the blood, and, in effect, it is demon- 
strated, to-day, that prussic acid acts with such terrible violence 
simply because it enters into combination with the haemoglobin 
of blood corpuscles, and hinders the incessant and necessary ex- 
change between the atmospheric air and the different organs of 
the body, and thus prevents in the system the arrival of oxygen 
and the elimination of carbonic acid. 

But in reality, with the exception of these volatile substances, 
all the other remedial or toxic agents act elsewhere than in the 
blood and not in this fluid itself. In the blood they are borne 
along side by side, and make the round of the circulation, with- 
out mixing, without acting, and without suffering notable modi- 
fications in their constitution or in their structure ; exactly as 
on the same telegraphic line a great number of currents pass 



ALBUMEN AND THE ALKALINE CHLORIDES. 265 

and each traces a despatch on its arrival, without the least con- 
fusion. 

These substances thus pass along unchanged in the blood, I 
repeat, because they are covered — as it were, encapsuled — in albu- 
men, just as are the globules of buttermilk. If it were not so, 
these small particles of butter would unite to form one large 
mass on the surface of the milk, instead of remaining in emul- 
sion. We know, to-day, that the existence of such a capsule 
prevents the junction of the globules and the formation of a 
mass ; whipping the fluid acts by destroying this capsule. 

These substances, which have thus made the round of the cir- 
culation, do not become permanently active, and do not suffer the 
modifications necessary at this point of view, before they become 
free, and this does not happen until they arrive in organs which 
do not contain albumen ; then these substances become free, as in 
the urine, in the cerebro-spinal fluid, in the fluid contained in 
the internal ear, and in the aqueous humor of the eye, and here 
in these liquids there is a recurrence of symptoms due to the 
activity of the drug which had first induced notable effects on 
the surface to which it had been applied. 

It is on this account, as I have already observed, that canthari- 
din circulates in the blood without manifesting its noxious prop- 
erties; on its arrival in the kidneys, the urine not being 
albuminous, it acts on these organs as a veritable blister, re- 
newing the effects it had produced on the skin. 

There are also other phenomena observed when these sub- 
stances, after being carried on in the blood, are exhaled into the 
liquids exempt from albumen, and thus come in contact with 
organs more or less sensitive; this explains why active substances 
like quinine induce such powerful effects on the auditory appa- 
ratus ; it is because in these situations they can act with their 
entire power and induce, in this particular case, toxic effects on 
the peripheral extremities of the auditory nerves, whence the 
appearance of vertigo and that spontaneous affection called 
Meniere's disease. 

Several objections may be made against this view of the Bub- 



266 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ject. It may be said that in the blood no effect is produced ; 
that all the chemical phenomena occur elsewhere than in this 
fluid. 

Claude Bernard has written that substances cannot act on the 
nervous centres, for instance, without having been introduced 
into the blood ; in this fluid, he said, they produce their effects 
during their passage through the organs. 

I think this opinion is not entirely clear, and furthermore, all 
the physiologists do not agree with the illustrious representative 
of the French school of physiology on this point ; M. Yulpian 
does not admit that the phenomena induced by the alkaloids take 
place while these substances contained in the blood are passing 
through the organs ; he admits, as I do, that these substances 
must arrive within the tissues of the organs themselves ; that 
there must be parenchymatous intussusception, in order that there 
may be a more or less durable combination between the histolog- 
ical elements of the part to determine the modifications they are 
called upon to produce. To sum up, the true explanation appears 
to be that atropia, or morphia or strychnia, placed directly on 
the nervous centres, will not induce the usual phenomena which 
they are susceptible of producing, unless the drugs are first ab- 
sorbed and then arrive later to act on the nervous centres ; this 
fact does not, by any means, indicate that this effect is produced 
in the blood, but simply that the production of these effects is 
possible only through the exchange taking place between the 
blood and the organs, and solely when the substance which is to 
act as a remedy or a poison arrives in the organ at the same time 
with the plasma destined for its reparation. But it has been 
said, or it may be said, for I foresee these objections, that the 
toxic symptoms are often absent until, by an artificial process, 
such as the administration of the iodide of potassium, the sub- 
stances are made to reenter the circulation in order to be again 
eliminated ; for instance, take mercury, after a certain period, 
when there has been chronic poisoning; you will no longer ob- 
serve the symptoms of stomatitis or of dyscrasia of the blood, 
which are among the prominent primary effects of the adminis- 



ALBUMEX AXD THE ALKALINE CHLORIDES. 2G7 

tration of mercury, and which we seek to produce in secondary 
syphilitic affections. But if you cause this mercury to reenter 
the circulation, you may, in a certain number of cases, see the 
symptoms of stomatitis reappear, and, commenting on this fact, 
it has been said that mercury, while contained in the different 
organs, causes no toxic symptom, but when brought back into 
the circulation such accidents immediately reappear; yes, cer- 
tain phenomena are produced, but no tremors or paralysis ; it 
thus acts in a peculiar manner on the plasma of the blood ; that 
is to say, that it is not impossible for substances to cause diverse 
phenomena while contained in the circulation j but the symptoms 
generally observed are those induced by the excretion of the 
drug. 

It is the same for the other effects which may be produced by 
poisons returning into the circulation, after being disengaged 
from the tissues ; symptoms induced by their excretion are always 
observed, but no phenomena of constitutional intoxication. 

A third objection : the serum from a blistered surface, when 
it contains a large quantity of cantharidine, is capable of deter- 
mining vesication. 

I was not aware of this fact until recently, and this objection 
would not have presented itself to me, for I had not observed the 
fact before commencing to use M. Lailler's cantharidin collodion 
for blistering ; this simply proves that when the quantity of 
cantharides is very large, and when the blisters act with great 
energy, there may remain a quantity of cantharidin in the free 
state. 

Are you not well aware that there is an immense difference 
between an acid salt, and a strong basic or a neutral salt ? 

Do you not know that when a large quantity of acid is added 
to a sulphate there is free sulphuric acid ? This is just what 
happens in the case of the blister, and although albumen has the 
power of hindering the action of substances when in excessive 
quantity, there is a part which becomes liberated. 

To resume: it is no longer doubtful (what I have maintained 
so long commences to be recognized as a verity) that the g] 



268 PRINCIPLES AND METHODS OF THERAPEUTICS. 

part of the effects produced by active substances introduced as 
medicaments into the economy are not produced outside of the 
circulation ; and that the albumen and the plasmin of the blood 
act only in a certain measure in opposition to the realization of 
chemical phenomena produced by active substances, and conse- 
quently do not entirely hinder the physiological effects which 
they may induce, since these last are obtained solely through 
physico-chemical transformations. 

There is always, at least, a modification in the structure of 
parts when physiological effects are produced ; for instance, sul- 
phuric acid enters into combination with a tissue and deprives it 
of water ; when it has effected cauterization, its composition is 
changed ; it has become a hydrate. The same is true of chromic 
acid, and of potash, which combine with the tissues. 

There are certain substances which only cede a part of their 
strength, as, for instance, the alkaloid of quinine, which is found 
almost unaltered in the urine, but is no longer quinine ; it has 
produced exceedingly marked therapeutic effects (which were 
considered absolutely impossible when its therapeutic action in 
fevers was first spoken of), but when collected from the urine it 
has lost a part of its strength, and has become quinidia and 
quinicine. Then, whether substances suffer change or lose 
strength, the fact is certain, they cannot induce physiological 
effects without suffering some change in their composition or in 
their structure. 

In order to complete the study of a molecule (as has been 
done of a crumb of bread), and to bring to light the various 
changes it suffers in the economy, it will be necessary for me to 
speak to you of the introduction of this molecule into the paren- 
chyma of the different organs, of the duration of its sojourn, of 
its reabsorption, and of its elimination by the various emuncto- 
ries. 

But there exist difficulties in the demonstration of such a 
subject, which cannot be properly understood unless one has 
deeply studied these questions. On account of these difficulties 
I will demand your permission to take an example, and when by 



AKSENIC. 269 

particular care I shall have demonstrated to you the case of one 
particular drug, I am convinced that you will understand better 
the general laws governing the physiological effects which take 
place in all. 

There exists a drug which presents itself naturally to us, on 
account of the interest it has excited in therapeutics, the high 
importance it has acquired in medical jurisprudence, and the 
researches made concerning it. I shall attempt, with the aid of 
this substance, to make you understand the modifications which 
medicaments suffer in the organism, and what temporary distri- 
butions they undergo. The substance of which I speak is 
arsenic. The subject itself is extremely interesting, and you all 
recall vividly the particulars of a case which has recently much 
moved the public mind. 

I am of opinion that the history of arsenic, made in detail, 
will be useful to you ; and I wish more particularly to present 
the subject to you, in order to associate the therapeutical and 
medico-legal sides of the question, and to thus inform you of a 
number of errors generally received concerning this drug, as 
also to lay before you a certain number of new facts j some be- 
longing to myself, others collected from various observers, and 
which all give a peculiar interest to the question. AYe will then 
consider arsenic. The pharmaceutical form has little importance 
for this drug, and this is generally true of the minerals. When 
organic matters are to be used it is indispensable to introduce 
them in certain forms, and with the most perfect structural in- 
tegrity obtainable, because they differ, often, one from the other, 
solely by loss of their dynamic properties. For mineral sub- 
stances, on the contrary, the form under which they arc intro- 
duced matters little ; it is the mineral element contained that 

acts. 

Arsenic, a metalloid, acting by itself, can be introduced in 
any form; the same formation of therapeutical phenomena will 
bo observed, and the sole difference will be the aggravation or 
diminution of effects produced by different preparations. 

Arsenic, it may be first laid down as a general fact, is a poison for 



270 PRINCIPLES AND METHODS OF THERAPEUTICS. 

both kingdoms ; it is a poison for all animals — there are none 
which escape its influence ; but it is," also, a poison for the vege- 
table kingdom ; a plant watered with it will perish. There is, 
however, one strange exception to this rule (the greatest crimi- 
nals have friends) ; arsenic has for friend a plant unable to live 
except among substances containing this poison. There is de- 
veloped in arsenical liquids a form of algae which has particular 
characters, always the same ; it is formed of bulbous articula- 
tions, in this respect somewhat resembling those of the muce- 
dines of thrush ; it is, if you will, a leptomitus, or rather a 
hygrocrocis. With this single exception, arsenic is, I repeat, 
a poison for all things possessing life, no matter to what 
kingdom they belong. It is an anti-zymotic or anti-ferment, as 
ferments are organic substances, even possessing an inferior 
degree of organization. But it is not sufficient to prove 
scientifically that a substance is an anti-ferment ; it is necessary to 
know why it is so. This we know concerning certain substances, 
but why arsenic is antiseptic has not yet been determined. 

What we do know is, that arsenic, which destroys the large 
organisms, destroys also the smaller, and even the globules; this 
explains readily a strange fact observed by those interested in 
medical jurisprudence: that in the bodies of those who have suc- 
cumbed to the influence • of arsenic the parts which have come 
in direct contact with the poison remain for weeks almost un- 
changed; the digestive organs are found in a state of remarkable 
integrity, while the rest of the body is in a state of putrefaction, 
an effect due to the antiseptic properties of arsenic. 

It acts in the same way as an escharotic. I have just ob- 
served that it destroys the inferior organisms; it destroys also 
the histological elements of apart; it is not a caustic substance, 
but it produces a scar like a caustic; it does not produce an 
eschar by carbonizing the substance of an organ, or by trans- 
forming it into xantho-proteic acid, or into a soap ; it kills it. I 
do not contend that it acts without producing any modification, 
but the part is not so profoundly modified as to be difficult of 
recognition. 



ARSENIC. 271 

la 1877, I repeated an experiment which I had also previ- 
ously made; and which demonstrated that the eschar produced 

by arsenic contains the histological elements of the tissues; if in 
a muscular region, the muscular fibres are distinguishable, but 
they have lost somewhat; no striation is found when the part 
has contained voluntary muscles; when, on the contrary, the 
eschar has been produced by sulphuric acid, nothing remains 
but a magma without form, and no longer containing any trace 
of histological elements. 

Arsenic, then, exerts simply a toxic influence on the part of the 
organism with which it comes in contact; it can no longer live, or 
if small doses have been used it lives under adverse conditions. 
This explains why arsenic as an escharotic has been regarded 
with so much favor; it seemed almost possessed of intelligence 
when it was observed how it attacked the different layers in the 
productions of new formation called cancers, and respected the 
neighboring healthy tissues. 

Its intelligent discrimination in attacking tissues is, you under- 
stand, but a question of the proportion or quantity administered; 
when it comes in contact with a tissue well supplied with blood- 
vessels, it is partly carried off in the circulation, and there is 
never a sufficiently large quantity present to produce death of 
the part; in tissues not so well irrigated it is, on the contrary, apt 
to accumulate; it spares, then, the living tissues, but acts on the 
others when there is a great accumulation of new cells, as in en- 
cephaloid cancer. We will now consider the effects of this poi- 
son when it is placed in contact with the cutaneous surfaces, or 
when it is introduced into the stomach to pass from it into the 
circulation and thus enter the different tissues. When arsenic is 
placed in contact, in small quantity, with the skin, it determines 
a number of phenomena which are sometimes of considerable 
importance; for instance, redness, with sufficient heat to become 
disagreeable, is induced, and an eruption may ensue ; when the 
intensity of its action is greater, this eruption consists in the de- 
velopment of pimples; the expression is not very scientific, but 
it nevertheless expresses the condition of things ; a slight reaction 



272 PRINCIPLES AND METHODS OF THERAPEUTICS. 

against the irritation determined by the arsenic takes place, and 
these pimples are the expression of the analogous inflammation 
which takes plaoe to aid in the elimination of an eschar when 
produced by a caustic. But ulcerations may be produced if the 
quantity of arsenic is more considerable, and they may occur on 
the skin or on the mucous membranes ; sometimes they are ob- 
served on the genital organs, where they produce a rounded 
ulcer, resembling somewhat the primary ulcer of syphilis. 
Similar ulcerations are met with in the noses of those who work 
at the manufacture of Schweinfurt's green (paint), and sometimes 
perforation of the nasal septum occurs, as happens from contact 
with chromic acid. 

These phenomena are not observed during the therapeutical 
use of the drug, for a small quantity of arsenic is not thus dif- 
fused over the surface of the body, but they are often observed 
in workmen and in miners working in mines containing sulphide 
of arsenic, in those who manufacture Schweinfurt's green dye, 
and in the young women who manufacture flowers colored with 
this dye, a manufacture which has been prohibited by law ; and 
such lesions were also observed to occur to ladies wearing 
these flowers. I have myself seen such results where it was 
the fashion to wear these brilliantly colored green leaves. 
These accidents have occurred also to those persons wearing or 
fabricating malachite, and they may be observed in a certain 
number of cases where rooms are papered with green paper con- 
taining arsenic. 

But it must be admitted that the satined green papers have 
never poisoned anybody ; but only the velvety papers colored 
by Schweinfurt's green, and containing fine molecules of the 
drug, applied on the paper with a sort of glue, constituting the 
velvet on its surface, thus coating the small solid particles of 
arsenic ; it is easily understood that during the time the paper is 
dusted the currents of air carry through the atmosphere a more or 
less notable proportion of these molecules, which can be absorbed 
and determine the lesions they are capable of producing ; and 
this does not happen, I repeat, with green satined papers, or with 



ARSENIC. 273 

curtains colored with this green dye. In a recent case, where 
the window curtains contained arsenical green dye, they were 
doubled with fine muslin, which should have contained a small 
proportion of arsenic if the green fabric had caused the acci- 
dents, yet Marsh's test failed to show the presence of arsenic. 

Concerning this subject an interesting supposition has been 
proposed by a German experimenter ; he thinks that when the 
curtains or wall papers of a room are colored by arsenical green 
dyes, in the confined atmosphere arseniuretted hydrogen may be 
formed; I think that there must be some mistake here, or, at 
least, that such is not generally the case. 

For the production of arseniuretted hydrogen, certain condi- 
tions (of reduction) are necessary, which do not habitually exist 
in the rooms we inhabit ; I have myself made known the possi- 
bility of the formation of arseniuretted hydrogen in arsenical 
mineral waters ; it is sufficient to observe the disagreeable odor 
of these waters when in a state of putridity, to recall the odor of 
arseniuretted hydrogen burning in the air ; that is to say, becom- 
ing oxidized. I called attention to this fact, explaining it by the 
reduction of the arsenic or arsenious acid (chemists admit that it 
is arseniate of soda), through their contact with the organic mat- 
ters depositing in putrefying water; to-day I might possibly say, 
taking into consideration the experiments of Planchud, which 
demonstrate that an algous plant, the sulphuraria, is capable of 
decomposing sulphate of calcium, that algous growths favor 
the formation of arseniuretted hydrogen. But, whatever may be 
the theory, it is certain that in order to form, with arsenious acid, 
arseniuretted hydrogen, the presence of certain substances to favor 
oxidation are necessary, which are not present under the condi- 
tions in which we usually live ; I contend, then, that it is not 
usual to encounter arseniuretted hydrogen in rooms where green 
wall papers are present. 

We can now consider the action of arsenic on the digestive 
organs; and here we will have to distinguish between the topical 
effect, the reflex phenomena, and the general or diffused ei 
qf the drug, as we always do in studying a therapeutic agent. 

18 



274 PRINCIPLES AND METHODS OF THERAPEUTICS. 

We will first consider its topical or local action ; and this is very- 
interesting as recalling a general physiological law, which is, 
that the drug produces different effects according to the surfaces 
with which it conies in contact. This shows that we resist the 
action of the drug, and that each organ reacts after a certain 
fashion proper to itself, and thus induces different impressions 
and sensations ; as, for instance, when arsenic is introduced into 
the nasal passages, it induces sneezing, by the sensation it de- 
termines on the parts ; placed in the mouth, gustatory sensations 
are experienced ; a metallic taste when there is a very small 
quantity, and when the dose is large, a burning, acrid sensation 
is induced in the throat ; and it is here that its topical influence is 
most considerable ; the same feeling is experienced in the pharynx 
and oesophagus when the poison descends. 

The substance arrives finally in the stomach ; what feeling will 
it there induce? Certainly no sensation of taste will be experi- 
enced ; the stomach is the seat of the sensation of desire for food, 
or appetite, and it is this sensation which is developed when the 
quantity of arsenic is small ; in other terms, the trifling sensation 
determined by the arsenic in the stomach causes the production 
of a desire for food, which is a normal sensation when proceeding 
from that organ. Naturally, if a more considerable quantity is 
ingested, symptoms induced by irritation, as sensations of heat, 
and of more or less burning pain, are experienced ; then other 
phenomena succeed, such as dyspepsia, with pain and conse- 
quently gastralgia, and if the dose has been still larger the indi- 
viduals suffer from nausea, followed by vomiting, which almost 
always happens ; these are the most characteristic phenomena of 
the action of arsenic. 

But I am obliged to observe to you that this symptom is not 
constant, and that there have been cases where arsenic was in- 
gested in such proportions that death ensued, and yet where 
vomiting never occurred, nor any of the symptoms of arsenical 
poisoning. You will find such cases mentioned by authors of 
great weight on this subject, and particularly by Taylor. 

Vomiting is, in fact, the result of an impression made on the 



ARSENIC. 



275 



peripheral extremities of the pneuniogastric, and is not determined 
necessarily by the irritation, or inflammation, or even by the 
ulceration of the stomach — all grave lesions of the organ. 

The emesis produced by arsenic is identical with that induced 
by tartar emetic, or ipecac ; there is a particular excitation which 
may be followed or not by its effects ; the excitation, even, may 
not be present, as paralysis of sensation, or even of motion, may 
occur in the interior organs, just as in the peripheral organs, and 
for the organs connected with nutrition of the organism just as 
for those connected with the functions of relation. There are 
cases where the stomach is devoid of feeling, and others in which, 
though common sensibility be present, there is not sufficient re- 
action to produce emesis; this happens in certain pathological 
states. 

I will defy you to produce emesis in subjects in a low typhoid 
state, where pulmonary congestion is diagnosed, and where it 
would be advantageous. I have never succeeded; and why is 
this so ? Because, perhaps, common sensation is wanting, and to 
produce emesis the cooperation of all the thoracic and abdom- 
inal powers are necessary, and besides the contractility of the 
stomach itself, complete integrity of the nervous system and of 
the organs are necessary; and though these conditions may exist 
at the moment the poison is introduced, they may disappear 
through the state of prostration in which it throws the subject; 
this is the reason why no vomiting is observed in some cases, 
though the drug may have caused death. 

Besides these symptoms and the phenomena which accompany 
them, there are others due to the irritation which the poison 
produces in its passage from the stomach to the end of the di- 
gestive tube. This irritation causes various changes, according 
to the intensity of the action of the poison ; sometimes simple 
redness, at other times extremely marked redness, with ecchy- 
motic spots, even inflammation, with softening of the mucous 
lining; and, finally, if the patient has survived longer, ulcera- 
tions, left after the elimination of eschars. You see, then, that 
according to the period at which the examination is made, and 






276 PRINCIPLES AND METHODS OF THERAPEUTICS. 

the quantity of the poison ingested, you will have different 
phenomena. 

The reflex phenomena determined by inflammatory action 
supervene later, but these do not show that absorption has taken 
place, and you will see that it is indispensable to distinguish the 
lesions produced by sympathy from those supervening after 
the diffusion of the drug, on account of the great importance 
such discrimination may present in a medico-legal point of view. 
The modifications produced on the stomach are of no conse- 
quence, unless the sensibility of the organ is intact and it has 
the necessary power for the production of emesis. As I 
have just said, there are cases where no emesis takes place, and 
if, under the influence of arsenious acid, symptoms of collapse 
are produced, following its absorption and not preceded by re- 
action of the system, you may witness the evolution of all the 
symptoms of poisoning without any of the characteristic signs, 
such as nausea, vomiting and alvine evacuations. I have just 
observed that if the effects do not prove immediately of so much 
gravity, there are more or less marked symptoms of irritation, 
and, as post-mortem examination has shown, softening may be 
found, more or less circumscribed, in different points, and even 
ulcerations, when these softened points (this change being analo- 
gous to the formation of an eschar on the periphery) have been 
eliminated. 

At the same time that these effects are produced there is a 
repetition of the efforts to vomit, or, perhaps, oftener, to go to 
stool, and a profuse diarrhoea is observed to come on, with re- 
peated evacuations of matter, which varies according to the 
period at which the affection has arrived. 

At first, fecal matters, simply softened, are ejected; then serous 
matters, and even rice-water discharges, and, finally, phenomena 
resembling those seen in dysentery are observed, which co- 
exist with or are induced by the ulceration of the stomach and 
intestines ; pure blood and matter resembling coffee grounds are 
passed, as in simple ulcer. Such are the phenomena which 
arsenic determines in this portion of the digestive tract. But 






AKSENIC. 277 

there are other general phenomena induced through the influence 
of these local changes on the entire system ; these are called 
sympathetic or reflex. 

It is not possible that such disorders be produced in the mu- 
cous membrane of the stomach and intestines without inducing 
choleriform symptoms, which, as you know, exist in all cases of 
poisoning by acrid substances. You will observe that sub- 
jects presenting such lesions offer the following symptoms : the 
face is haggard, the eyes often appear sunken, a black circle is 
traced under the eyelids, and the face is more or less pallid ; this 
appearance has been considered a necessary adjunct in cases of 
poisoning, but it is observed solely when these grave lesions 
have been produced ; otherwise, when the lesions are not marked, 
nothing similar has been observed. Next, haggard face, pros- 
tration, loss of strength, and at the same time, profound troubles 
of the various functions — respiration becoming difficult, the pa- 
tient feeling a weight oppressing him, with disorders of the cir- 
culation — the pulse becomes small and thready, later it becomes 
slower, then the sense of frigidity, at first local, becomes general, 
the nails are cyanosed ; then you see suppression of the urinary 
secretion ensue, as in cholera ; but these phenomena are observed 
in every case of poisoning, and afford no indication of the nature 
of the poison. If sulphuric acid is introduced into the stomach, 
those same choleriform symptoms ensue which are observed after 
all lesions affecting the digestive tube or the innervation of the 
pneumogastric. 

There are other very singular phenomena occurring at this 
period ; convulsions and spasms are observed, and true tetanic 
symptoms may supervene. Tetanus is, as you know, a very grave 
affection which sometimes occurs as a complication in lesions of 
the extremities and of the abdomen, for other traumatisms are 
much less frequently followed by its appearance. This is a 
very curious fact ; and often when ovariotomy has been per- 
formed, the women succumb to tetanic spasms; this fact might 
find an explanation in the existence at the periphery, in the ex- 
tremities, and in the abdomen also, of corpuscles of Pacini, 



278 PKINCTPLES AND METHODS OF THEKAPETJTICS. 

which are more numerous under the peritoneum than elsewhere; 
whether this be the true explanation or not, it seems to me an 
interesting anatomical fact to mention. 

Now, after having spoken concerning the local action and con- 
cerning the effects induced in the general system by sympathy, 
I will consider the action of the drug when diffused in the or- 
ganism. I will study separately the effects as induced by small, 
moderate, and large doses. As relates to small doses, they are 
generally not very offensive in their effects ; they are introduced 
for the hygienic or therapeutic action ascribed to small doses. 
You all know the account given by Tschudy of the toxicophagi, 
or rather, arsenicophagi, inhabitants of Styria, of Carniola, and 
of lower Austria, who imitate the custom of horse sellers, and 
in order to improve their personal appearance and give them- 
selves certain qualities wanting in their race, are accustomed to 
take more or less considerable doses of arsenic, or rather, of 
arsenious acid. 

I have placed these facts under the category of small doses, for 
they take small doses, as 1 or 2 centigrams (one-fourth of a grain) 
per diem, augmenting gradually the dose ; the picture traced by 
the observers of these individuals appears to me too flattering ; 
it is said that they acquire great strength, have remarkable 
agility, climbing the steepest mountain sides ; while they were 
easily put out of breath before taking arsenic; in fact, they are 
said to feel like flying, as they express it themselves ; as for the 
young girls, they become veritable rose-buds, as colored as 
ripened apples; they acquire flesh even; and as fine skin is 
never seen in thin people, over bones thinly covered, their skin 
becomes clearer and more transparent. But, unfortunately, there 
is a dark side to the picture; arsenic does not always give such 
admirable results, and when these individuals come to require 
considerable doses serious effects may ensue ; so much so, that 
Tschudy, the great panegyrist of this habit, avows that a certain 
number of subjects become sick and end in marasmus ; he con- 
siders that such persons have not properly taken the drug ; but 
it is certain that many lose flesh and that some are affected with 



ARSENIC. 279 

paralysis, due to the action of the poison ; this happens rarely, it 
is true, for generally they possess sufficient sense not to take 
large enough doses to induce such noxious effects. But I wish 
to inform you that five or ten centigrams (from three-fourths 
to one and a half grains) cannot be taken day after day with 
impunity, or without producing evil effects, although such has 
been asserted to be the case. 

I come now to the uses of the drug in therapeutics ; and I 
will first speak concerning the small doses which we generally 
give, such as from five and ten milligrams to five or ten cen- 
tigrams ; when these doses are employed no great effect is at 
first perceived; perhaps a slight increase of appetite, and in 
certain cases slight thirst, are experienced, but no phenomena in- 
duced by the diffusion of the drug through the system ; but when 
these doses are repeatedly given, for a considerable time, then 
the effects are marked, and particularly in morbid conditions. 

You are aware that in the physiological state the economy is 
possessed of so much elasticity that it does not obey or is 
not easily affected by substances introduced: while, when there is 
a more or less diseased condition, the morbid phenomena which 
a poison or medicament is capable of producing are manifested 
in full force. When patients are in a febrile state, as in tubercu- 
losis, the following phenomena are observed when arsenic is 
taken : a falling of the temperature has been mentioned j it has 
been observed, and to a notable degree, but it is not accompanied 
by a marked descent of the mercury, as happens after the 
administration of such substances as quinine or digitalis. 
Nevertheless, there is a slight reduction of the temperature, 
but it is only when large doses are introduced, or when there is 
chronic poisoning by arsenic, that very notable diminution of 
the temperature is observed; moderate doses.reducc the tempera- 
ture perhaps one-half or one degree. There is also a diminution 
in the number of pulsations, and this is well marked in phthisi- 
cal patients; some sedation of the heart is produced, not only 
in the number, but also there is diminution in the violence of its 
contractions, and this diminution of the intensity of the con t rat - 



280 PRINCIPLES AND METHODS OP THERAPEUTICS. 

tions is so considerable that they become normal, and the im- 
pulse felt at the apex is much less violent. 

These facts are indubitable to-day. Even when there is no 
fever the action of the heart may be moderated under the influ- 
ence of arsenic. Furthermore, when careful examination is made 
it will be found that a diminution of the quantity of urea coincides 
with the fall of temperature. It has even been advanced that 
there is a diminution at the same time of carbonic acid ; that is, 
that the quantity of urea which is at the highest state of oxida- 
tion to which nitrogenized matters can arrive is reduced at the 
same time with carbonic acid, which is the last term of oxida- 
tion of ternary bodies ; consequently there would be a diminution 
in the burning up or oxidation in the system of combustible 
matters, no matter what they may be. 

To resume, you can see of what importance arsenic may bo- 
come, particularly if this last property be admitted ; for if it 
were absolutely demonstrated, it is evident that there would be, 
after its administration, a reduction in the combustion going on 
in the system. 

But because there may be a diminution in the quantity of 
urea excreted, we must not too hastily conclude that there is re- 
duction of the entire combustion going on in the system ; there 
may be an increase in the combustion of ternary substances. 
But if we had also a diminution in the quantity of carbonic acid, 
the fact would be proved. Under the present condition of 
science on the subject, it may be said that there is a reduction of 
functional activity of all the great organs, and not only that 
there is diminution of the combustion, but also a reduction of 
the activity of tissue formation and decomposition or absorption, 
and hence reduction of temperature. When phthisical patients 
are under the influence of a febrile state, caused and kept up l^ r 
the existence of localized lesions, if arsenic is administered there 
is diminution of fever and possibility at the same time of amelio- 
ration, since there is less active denutrition through the lessening 
of the febrile symptoms. 

To return to our consideration of the toxicophagi, or arsenic 



ARSEKCC. 281 

eaters, I think that the individuals benefited by arsenic are those 
generally who have slight fever, such as chlorotic patients (febris 
alba virgimim), with whom it is sufficient to arrest excessive 
denutrition and exaggerated combustion; and this is exactly 
the effect produced by arsenic when it improves the personal 
appearance of subjects who are in the condition I" have men- 
tioned. 

This is the opinion I have always held and defended : that 
arsenic is an agent which has a sedative effect on all the phe- 
nomena of hsematosis, of respiration, combustion, and also on 
those phenomena induced by morbid irritation in pathological 
states. 

This is not the opinion which has been always held, even in 
this school; thus, in 1865 the opposite opinion was maintained, in 
a long article on asthma,* and it was founded on a small number 
of experiments made in foreign schools, where, under the influ- 
ence of arsenious acid, a diminution of carbonic acid had been 
observed; this conviction had become an article of faith with 
some persons, and it was said that arsenious acid augments the 
combustion in the system, and thus increases the state of denu- 
trition, or decomposition, as also of formation or composition of 
the tissues, and that through this exaggerated condition of reno- 
vation the body renewed itself; to-day this opinion is no longer 
considered of any value. 

Now we come to the consideration of moderate doses — of one, 
two, or three centigrams. These are doses often given in intermit- 
tent fever. Thus Boudin, and all that school which made more 
or less use of arsenic, often gave up to five centigrams in inter- 
mittent fever, and I believe it is the sole method of efficaciously 
combating this fever with this drug; as for the other febrile 
states, such as are observed in phthisical patients, they are 
moderated by smaller doses. 

But when it is necessary to treat the intense attacks of fever 
caused by miasmatic influence, of so much gravity as those 

* Germane See: " Nouveau Dictionnaire de Med6cine et Chirurgie Pra- 
tiques." Paris, 1865. Article, "Asthma;" 3d vol., p. 583. 



282 PRINCIPLES AND METHODS OF THERAPEUTICS. 

treated by Boudin in Algeria, then small doses have little effect, 
and it is necessary to prescribe almost toxic doses, producing the 
state of collapse, of which I have spoken, and inducing acci- 
dents more or less approaching the choleriform symptoms. 

I confess, I have not had any success, for I am not one of those 
who give large doses of arsenic, except in one single case, where 
a somewhat large dose had been administered ; the patient fell 
into a state of prostration, which I had not desired to produce, 
but from which he profited. We will then consider doses of one, 
two, or three centigrams. With the exception of a few symptoms 
of intolerance, which are manifested in delicate subjects, the 
same phenomena which I have already described occur in the 
circulatory system ; generally, there is a tendency to reduction of 
temperature, but insufficient when it is necessary to act on an ac- 
cess of fever of any gravity. But certain other phenomena, those 
of elimination, are observed also, which do not appear after small 
doses. So that there are not many symptoms of trouble in the 
digestive organs — a slight intolerance; no troubles of the general 
system ; but when these doses are continued, phenomena induced 
by elimination from the emunctories ensue; and these last may 
exist after very feeble doses, but are more marked when the 
moderate doses of which I now speak are taken. 

A small quantity of arsenic induces, very often, marked diure- 
sis, a veritable hydro-diuresis, j ust as is induced by acetate of 
potash. In a certain number of cases the contrary effect is pro- 
duced ; the quantity of urine is lessened, there is oliguria, and 
you will be able to recognize beforehand what will ensue. I 
have given you the general rule : In all cases where the kidney 
is in the normal condition, and is not congested, if a substance 
capable of exciting the circulation is injected into it this excita- 
tion shows itself by an increase in the quantity of the urine. 

When, however, the organ is in a congested state, and there is 
already considerable passive tension, if the same substance which 
just now caused diuresis is introduced, it increases the intensity 
of the hyperemia, which may have been on the border of actual 
inflammation. Veritable phlogosis is thus produced, and partial 



ARSENIC. 283 

and even complete suppression of urine ensues. This fact should 
be remembered. 

In the liver, analogous symptoms have been observed ; in cer- 
tain cases, after sensations of malaise and of plethora in this 
region, bilious diarrhoea is observed ; it is the arsenic passing 
by the liver and causing irritation. Similar phenomena are ob- 
served on the integuments ; eruptions more or less marked occur 
on the skin, and under varying forms ; sometimes it is simply 
irritation, provoking itching; then, again, small pimples or vesi- 
cles are observed. Then, when it is a chronic skin affection that 
it is desirable to modify by arsenic, a grayish tinge, on which M, 
Hardy has insisted, is observed. This tinge seems to be the 
result of an exaggerated deposit of pigment, but it is really due 
to the deposit of the metallic substance, as in poisoning by silver 
or lead. Sometimes a veritable erythema is produced. 

This same effect, which shows itself on the skin by the lesions 
I have mentioned, is manifested by somewhat similar troubles 
on the eyelids. There is redness and an exaggerated secretion 
from the glands of Meibomius ; the eye itself is sometimes con- 
gested, as in this region there is always a tendency to the exha- 
lation of serous liquid in the interstices of the cellular tissue 
whenever any morbid condition is present ; oedema palpebrarum 
occurs, as it does in all the inflammations of the eyelids or eye. 
The oedema arsenicalis is, then, nothing peculiar under these 
conditions. 

The mouth is similarly affected. Eruptions are not seen, as on 
the skin ; they are modified on mucous membranes, on account 
of the anatomical differences between the parts; but sub-inflam- 
matory states, with exaggerated secretions, and in certain sub- 
jects, salivation, even, may ensue. 

In cases where toxic doses have been taken such abundant sal i va- 
tionhas been observed, and accompanied with a certain degree of 
gingivitis, that those who have witnessed it have been often mi- 
taken, and considered it as a case of mercurial stomatitis, and 
with greater show of reason, the secretion, etc., being extremely 
fetid. This is a fact which I desire to call to your attention ; we 



284 PRINCIPLES AND METHODS OF THERAPEUTICS. 

are accustomed to see mercurial stomatitis accompanied by so 
repelling an odor that it is difficult to approach the patients. But 
how is this odor produced ? It is not caused by the condition of 
the mouth, nor by the animal substances submitted to the influ- 
ence of the saliva; there must then be some peculiar matter pres- 
ent, perhaps some compound in which the metal has its part, and 
which is constituted by one of the numerous radical bodies with 
which we meet so often in the combinations of organic substances; 
this same phenomenon takes place with arsenic and with lead. 

I come now to the consideration of large or toxic doses ; and 
the doses are of this character when they approach or reach five 
centigrams. As I have already told you, accidents ensued when 
these doses were given in intermittent fever ; and, in effect, when 
the above dose is exceeded grave accidents may supervene; first, 
there is exaggeration of all the phenomena which you now know 
to be produced by arsenic; then more or less severe pains are 
experienced in the limbs, and tremors, convulsions, convulsive 
twitchings, and even, sometimes, tetanic contractions may be ob- 
served. The trouble in the nervous centres is manifested by 
symptoms of excitation, by delirium; and this delirium may be 
intense, lasting, not hours, but days and even weeks, and compro- 
mising existence, for death may ensue, just as in an ordinary 
inflammation of the meningeal coverings of the brain. 

Sometimes opposite symptoms appear ; want of sensibility in 
the muscles, and paresis, and even veritable paralysis, may come 
on ; and then, instead of the delirium, coma may be observed ; or 
sometimes delirium and coma alternately, and death arrives while 
the patient is thus suffering. I will not return to the considera- 
tion of the reflex phenomena, for they are present when mod- 
erate doses were used ; but in conjunction with them the grave 
troubles I have just mentioned occur when large doses are ad- 
ministered, and then only. 

One word on paralysis of arsenical origin ; and here again the 
subject is very interesting ; it can be affirmed that to-day the 
history of arsenic presents a great number of new facts, which, if 
well known, would render the opinions of experts in medical 



ARSENIC. 285 

jurisprudence much more reserved in the interpretation of cases 
submitted to them. I affirm, then, that arsenical paralysis exists, 
and I made mention of the fact in considering the hygienic use, 
in small doses, of the drug. 

These facts occur commonly enough, taking into consideration 
that arsenical poisoning is not an every-day occurrence ; they are 
not, however, often published. Nevertheless, M. Hipp Barella,* 
physician in the vicinity of Namur, has been able to collect 
twenty-nine cases ; and these facts are known only since the 
eighteenth century ; yet a certain number of authors, and among 
others my respected colleague, M. Jaccoud, seem to doubt the 
existence of paralysis of arsenical origin. But it certainly exists, 
for I have observed its occurrence in a case of voluntary arsenical 
poisoning. A woman, having many causes of anxiety of mind, 
poisoned herself with about a coffee-spoonful of arsenious acid, that 
is, with about seven or eight grams; the symptoms which ensued 
were formidable, and she seemed several times about to suc- 
cumb, but I saved her, orrather aided in her recovery, and she en- 
joyed tolerable health afterward. Very well ; in her case there was 
paralysis of all the four limbs, resembling very much saturnine 
palsy ; but afterwards, instead of the flaccidity observed in lead 
palsy, there was a sort of retraction of the flexor muscles, which 
were not paralyzed, while the extensors were affected in j list the same 
order as when caused by lead poisoning; and the forms of para- 
lysis are so nearly identical that, one day, when Duchenne, of 
Boulogne, was in my service, I indicated the patient to him as a 
very interesting case of lead palsy ; he examined her with care, 
by electricity, and returned to me saying : " Yes, it is a fine case 
of saturnine paralysis," and was very much astonished when I 
informed him it was not. Christison has remarked that arseni- 
cal paralysis very much resembles lead palsy. I consider that 
in some cases the two forms of paralysis may be identical 

You can easily see that this is a very interesting phenomenon, 
for it shows that there are general laws in pathology, as in thera- 

* Barella, de l'emploi thcrapeutiquo do 1'arsenic. New edition. Brus- 
sels, 18G6. 



286 PRINCIPLES AND METHODS OF THERAPEUTICS. 

peutics, and that if certain muscles and certain collections of 
muscles are affected by lead ; it is not because lead acts specially 
on them, but because there is a predisposition in certain muscles 
to be modified by all foreign substances acting on the nervous 
system. There are muscles predestinated to these forms of para- 
lysis; and it is a remarkable fact, to which I called attention 
twenty-five years ago, that it is the extensor muscles which are 
always affected in convulsions or paralysis; they are the most easily 
influenced. The flexor muscles, on the contrary, resist more ; not 
only are they not easily paralyzed, but it is difficult to induce 
convulsions in them ; you have remarked that in tetanus it is 
always the extensor muscles which are contracted ; and when we 
reflect, the extensor muscles are the most feeble ; both anatomy 
and physiology demonstrate this to be the fact. During the 
evolution of the new being the body of the foetus is drawn to- 
gether, or flexed upon itself; and during intra-uterine life it is 
the strongest muscles which come into play ; and these muscles 
are not so easily affected by toxic agents ; they are not so easily 
convulsed or paralyzed as the others. 

A very interesting point in the history of the various medica- 
ments, which concerns therapeutics and also medical jurispru- 
dence, is to know whether arsenic accumulates in the organism ; 
some observers say yes ; others, no. I consider that it depends 
very much on the condition of the subject to whom it is given; 
in certain conditions there will be accumulation of doses and of 
action also, while under other and opposite conditions of the 
system this accumulation will not take place. What, then, are 
these conditions? When the subject is in good health, and has 
been surprised in good conditions of the system, when, also, the 
kidneys are normal, there is no accumulation. And this is easily 
understood ; the valve is open, the kidney is ready for the issue 
of foreign matters, the filter allows almost all the substances en- 
tering it to pass. If, then, no doses large enough to prove speed- 
ily fatal are introduced, there is a possibility that not the least 
accumulation will take place, and that just as the substance 
enters, so it will be excreted by the various emunctories. 



AESENIC. 287 

Suppose a case under opposite conditions — kidneys which do 
not perform their functions properly ; suppose a subject affected 
with interstitial or parenchymatous nephritis, or a diseased state 
of the kidneys from the presence of amyloid matters. This 
subject will be delivered over to a poison which he cannot rid 
himself of; the urine is in small quantity, and will not possess 
the power of eliminating the poison. Here, then, are exactly 
contrary conditions, and in which different and contrary phe- 
nomena will take place. Now, will there be accumulation ? What 
does the expression signify ? A distinction has been made between 
the accumulation of action and the accumulation of doses. I be- 
lieve that both amount to the same thing in the end. Accumulation 
of doses signifies that there is accumulation of the substance in the 
(prima? vise) digestive organs, as happens with strychnine pills, 
which do not dissolve readily, but some day dissolve all together, 
producing symptoms of more or less gravity. Accumulation of 
action — which signifies that the medicament passes into the 
parenchyma of the different organs and accumulates there — and 
the quantity taken up by the work of absorption and eliminated 
not approaching sufficiently the quantity of the substance in- 
gested, there ensues accumulation in the histological elements of 
the tissues. But, as you can readily see, there is always accumu- 
lation of doses or quantity. 

For how long a period does the elimination of arsenic last ? 
Another very important point for consideration. It is clear that 
if the drug is administered constantly this period may be in- 
definite ; but, naturally, we suppose that the important point is 
the duration of the elimination after its administration has been 
stopped, or after one very large dose has been taken; concerning 
this point there is great divergency of opinion among different 
observers; a certain number believe in a too rapid elimination, 
and consider that the arsenic has disappeared after fifteen or 
eighteen days ; there are others who think that at least a month 
is necessary; Chatin and Orfila are of this opinion. I go 
beyond even this period; in the case of which I have spoken — 
where the patient had probably taken eight grams of arsenions 



288 PRINCIPLES AND METHODS OF THERAPEUTICS. 

acid — the suicidal act occurred on September 25th, 1864; the 
woman entered my service October 23d, that is, the following 
month ; on the 27th I caused an analysis to be made which 
showed a large quantity of arsenic in the urine ; consequently, 
as you see, that was thirty-two days after the poisoning. Another 
analysis was made thirteen days later, and arsenic was still found; 
consequently, I can assert that during forty-five days arsenic 
was eliminated in the urine. Nevertheless, on November 10th, 
another analysis was made, without revealing any traces of 
arsenic ; then recalling the experiments of Natalis Guillot, and 
Melsens, on November 15th or 16th I gave iodide of potassium, 
and then on the 19th another examination of the urine was 
made and a considerable quantity of arsenic found to be present ; 
and very moderate doses of iodide sufficed to bring this about. 

But this woman had presented symptoms which had their seat 
in the encephalic nervous centres, delirium alternating with pros- 
tration, and I found myself obliged to shave the head and make 
cold applications. Her hair grew again, and I thought, after a 
certain number of months, that it would be curious to know if 
the hair contained arsenic. The analysis of the hair, made eight 
months after the poisoning, gave a quantity of arsenic sufficiently 
considerable; and this fact has great medico-legal importance, 
for the hair is not destroyed after death ; as proof, you need but 
regard the hair on mummies, and consider the length of time it 
is thus preserved ; so that even after a century arsenic could be 
found in the hair of a person poisoned with any considerable 
dose of the drug. 



AKSENIC. 289 



CHAPTER XXIII. 
Arsenic ( Continued) . 

Its passage through the system : role of the liver ; plasma ; histological ele- 
ments. 
Topography of arsenic in toxicology ; death by arsenic. 



Gentlemen : • 

Now that we have seen arsenic enter the system by different 
channels, and leave it more or less modified ; it remains for us 
to know what organs it has traversed and what route it has fol- 
lowed, after entering the organism. 

We will, then, attempt to follow step by step in its progress, 
the arsenic introduced into the digestive organs, which is its 
usual entrance. 

Arsenic is first taken up by all the vessels, of whatever 
description, which belong to the digestive tube. It is taken 
up by the lymphatics, by the portal venous system, and is found 
naturally in the ante-hepatic or cis-hepatic vascular apparatus ; but 
from the digestive organs it is particularly carried off by the 
radicles of the portal vein. 

It encounters, in its passage, the liver, an enormous gland, 
which has, in my opinion, a similar action, with relation to poison- 
introduced into the digestive organs, to that exercised by the 
lymphatic glands on poisons introduced through another channel. 

You know what Eicord has learned in relation to the buboes 
which are produced successively in the vHnity of the primary 
sore. 

These buboes arrest the specific pus in its passage, and it is 
even true that if they are opened and cauterized there is a possi- 
bility that ulterior general infection may not ensue, the specific 



290 PRINCIPLES AND METHODS OF THERAPEUTICS. 

poison having been arrested in th^ nearest collection of lym- 
phatics. 

You can, perhaps, call to mind the recent researches of M. 
Colin, of Alfort, who has demonstrated that the glands placed 
on the passage from the primitive lesion of malignant pustule 
(le charbon) arrest the specific matter peculiar to this dis- 
ease once, twice, three times, and they always oppose a new 
obstacle to its introduction into the general system. Very well ; 
in my opinion, the liver acts in a similar manner, and like these 
glands, arrests in their passage toxic substances introduced, acci- 
dentally or with criminal intent, into the digestive organs. 

We will see later on in what manner the liver is thus enabled 
to arrest these substances, and in what part of the gland arsenic 
and the other poisons are arrested. 

Arsenic, then, enters the blood vessels and is carried into the 
general circulation. How does it act when thus contained in the 
blood ? We observe, first, the great general fact on which I 
insist, that arsenic, like other substances foreign to the economy, 
is primarily incarcerated in the plasma and in the albumen, and 
has very little activity while in circulation in the blood. Never- 
theless, I have £aid that opinion on this subject should be some- 
what reserved, and I have shown you that when the quantity of 
the noxious principle was very considerable, and in too large 
proportion to be completely neutralized by the plasma, a part 
remained in the free state just exactly as acid in excess in a salt 
will have the same action as free acid. 

Something similar takes place for these more or less unstable 
combinations into which noxious principles enter with albumen. 

I have shown you that cantharidin, having passed into the 
serum of a blister, could act again on the skin of another region 
in the same individual, or even on the skin of another ; but the 
quantity of cantharidin must be enormous to have these effects. 
Very well ; a similar phenomenon takes place in the circulation ; 
when the quantity of the active principle is very considerable, it 
may produce toxic effects even while contained in the interior of 
the organs of circulation. 



ARSENIC. 291 

And as for arsenic, it is admitted that while in the circulation 
it may contract with the haemoglobin a combination similar to 
those into which it enters with the noxious principles, and that 
this action on the globules may show itself by phenomena of 
sedation and of diminution of hsematosis. 

There result, then, symptoms showing a lessening in the per- 
formance of the duties which these globules are called on to pro- 
duce. We get a better comprehension of this action of arsenic, 
by comparing it to that it exercises on the inferior organisms 
regarded as ferments. The globules can be compared to these 
protococci, and are similarly influenced by toxic substances ; so 
arsenic acts on them in a way to prevent them performing their 
functions. But there is a third stage : arsenic quits the vessels 
with the plasma, to penetrate into the histological elements and 
here have a new action. 

What effect does it have in this new situation ? Formerly it 
was considered sufficient to say, according to chemical analysis (this 
opinion dates particularly from the beautiful experiments of 
Orfila), that arsenic was stored up in a certain number of organs, 
and particularly in the liver ; and for a number of years the liver 
alone attracted attention in this relation. This was called a 
storing up, a condensation. The question is to know how arsenic 
is thus stored up or deposited in the liver, and how this gland 
happens to contain, in general, a considerable proportion, while 
there is little elsewhere. 

It was not discussed whether cavities existed in which the 
poisonous substance was thus condensed or collected, or whether 
the deposit occurred in the vascular system, in the lymphatics, or 
in the parenchymatous cells. It is very probable that arsenic, 
like the other poisons, is stored up in the lymphatic plexuses of 
the liver, and also in the cellular elements which constitute the 
secreting cells ; those which take from the blood certain materials 
which are restored again to this fluid, but solely after having re- 
mained a certain time accumulated in these cells. That is to 
say, that it is not simply an apparatus through which the blood 
passes, and which then excretes a serous fluid more or 



292 PEINCIPLES AND METHODS OF THEEAPEUTICS. 

charged with principles to be eliminated ; no ; these are cellular 
divisions, composed of voluminous cells, in which the principles 
ulteriorly destined to constitute the bile enter and remain a 
greater or less length of time. 

When you examine the hepatic cells in a normal liver, and 
more particularly when there has existed any obstacle to the 
circulation, you will find these cells more or less distended with 
biliary matters ; that is, biliary pigment. It is by dehiscence, 
irregular, it is true, that these products, which have been accumu- 
lated during a greater or less length of time in the parenchy- 
matous cells, are poured into the biliary canaliculi, to be 
transmitted thence into the more voluminous canals, and thence 
again into the gall bladder and intestine. 

I mention this to you in order that you may understand how 
it happens that poisons entering the liver remain there longer 
than in the other organs of secretion, and in particular, longer 
than in the kidney. They pass through the kidney without any 
delay; but they sojourn in the liver, for it is only by a sort of 
dehiscence that they are poured into the excreting canals. 

You can now easily understand how the quantity of the 
noxious principle is so considerable in the hepatic gland. 

How does this happen ? It may be thought that it simply 
penetrates into the intercellular substance in somewhat the same 
manner as iodine into starch. For you know that the iodide of 
starch is not a chemical combination ; the iodine infiltrates into 
the interstices, and when the iodide is reduced into thin layers it 
appears blue. Is it in this manner, or does arsenic enter into a 
veritable combination with the histological elements ? It cannot 
be doubted that it is a veritable combination, for in the hair, where 
I have demonstrated the presence of arsenic, there exist no in- 
terstices, but simply cones boxed up one within the other ; con- 
sequently, arsenic must have taken its place among the proper 
elements of this tissue. 

But, in 1865,* I demonstrated that arsenic, taking its place in 

* Gubler, " Dictionnaire Encyclopedique des Sciences Medicales ; " Ar- 
ticle Albuminuric. Paris, 1865. 



AESENIC. 293 

the tissues, was probably substituted for phosphorus ; and* I said 
that iu the situations where phosphorus normally predominates, 
arsenic should predominate when introduced through whatever 
cause. I applied to the introduction of arsenic into the histo- 
logical elements the great law promulgated by M. Dumas, the 
principle of substitution; that principle, in virtue of which 
any simple body belonging to a group takes the place of the sub- 
stance homologous to it in the same group, in the same way that 
a metal takes the place of hydrogen in organic compounds. 

I said, then, arsenic is substituted, and if it substitutes itself 
for any other body, it should be found in greater abundance in 
the tissues which contain phosphorus naturally. This opinion, 
founded simply on the consideration of chemical facts and laws, 
has been verified. "Within a short period, experiments very 
well made in this Faculty have demonstrated that, in effect, ar- 
senic takes its place, particularly in the nervous system. But 
the nervous system is distinguished from all the others by the 
presence of phosphorus in considerable quantity. You are 
aware that the chemists have shown it to be present in the entire 
nervous system, except in the parietes of the cells. 

That which Liebreich called protagon is, again, a substance 
containing phosphorus, and he considered it the most essential 
element of the nervous centres. He was preceded by Goblcy 
and other analysts, who discovered leceithin, which is nothing 
more or less than protagon. All these substances contain phos- 
phorus ; and you can see that I was right, and that experiment 
has demonstrated the correctness of my supposition. 

Thus you can very well understand that in searching for the 
presence of arsenic the nervous centres should be examined as 
well as the liver, for it is in these centres that it is met with in 
greatest quantity when there has been slow poisoning, or where 
poisoning has been produced by massive doses passing through 
the system during a certain period. 

But there is another and more general law. Arsenic does not 
remain solely in circulation in the blood and in the lymphatic 
system ; it is not deposited alone in the secreting elemente, and 



294 PRINCIPLES AND METHODS OF THERAPEUTICS. 

does not become substituted for phosphorus solely in the tissue, 
but wherever phosphates are present. 

Wherever there are phosphates there may be arseniates 
formed. Then, since phosphates exist almost everywhere, since 
they are found in all the liquids of the economy — for all serous 
fluids contain phosphate of soda, of magnesia, of calcium, as 
does the serum of the blood — arseniates may be formed every- 
where. Phospho-gly eerie acid is, say certain experimenters, in 
circulation in living organisms in combination with lime. 

Thus, phosphorus is everywhere ; it is deposited in the tissues, 
and is in circulation in the blood itself; but there is one system 
in which phosphorus is still more abundant ; it is the osseous 
tissues, in bone. You know that bone is constituted by the 
tribasic phosphate of lime, with other phosphates in small pro- 
portion. 

Arsenic substitutes itself for phosphorus in these combinations, 
and here is the proof: One day, when I was conversing on this 
law of substitution, with my learned friend, M. Paul Thenard, 
he said to me : "I have preceded you ; several years since I 
made the following experiments : I added to the food of certain 
young animals, which had been weaned, but were developing 
rapidly, a considerable proportion of tribasic arseniate of lime, 
in order to see what effect would be produced on their osseous 
system. I submitted them to this somewhat falsified system of 
alimentation, and then sacrificed them." 

Then, under these conditions, M. Thenard found that in the 
new layers of bony tissue the tribasic phosphate of lime was 
replaced by the tribasic arseniate. Can a more striking confirma- 
tion be found of this law of substitution, as applied to living 
organisms ? And you may thus understand how arsenic may 
remain so long in the system, since it enters into the constitution 
of bone corpuscles, and becomes a part of the organism itself 
during a very long period. 

The destruction or absorption of the elements is assuredly 
more or less delayed, more or less rapid j but for certain organs, 
such as, for instance, the hair, particularly in women, the process 



AESENIC. 295 

is very slowly accomplished. Consequently, you can see how, 
under these different conditions, arsenic may remain very long in 
the interior of the economy. 

Now, as we have considered the effect of arsenic on the liver 
and on the globules, what are its effects when it has penetrated 
into the histological elements? Two cases present themselves 
for consideration : In the first, arsenic penetrates slowly and in 
small proportions, and determines simply phenomena due to 
modification of action in different organs ; there is a falling off 
in the nutrition, comparable to the languid state of the circula- 
tion, and we see that the histological elements perform their 
functions in a less energetic manner. 

It seems, when the subjects affected are carefully observed, 
that there is simply a slowing-up in the functional activity of 
the various organs, in relation or in keeping with the languidness 
of the general nutrition of the body. It is thus that we can ex- 
plain the phenomena observed in arsenic eaters, and how the 
temperature is reduced in the febrile state, while, at the same 
time, the condition of the various tissues improve. 

But when the tissues are more rapidly invaded, as they are 
sometimes instantaneously, by massive doses, then the phenomena 
are different ; it is no longer a simple modification in the function 
(or the performance of the functions) of the various organs or 
of their nutrition ; symptoms of veritable poisoning of the his- 
tological elements take place ; there is a modification, not only 
in the rapidity or slowness of their evolution, but there is com- 
plete disorder, and the histological elements undergo a veritable 
arrest in their nutrition and evolution, or, at least, such diminu- 
tion that there results hindrance in the performance of all the 
great functions. 

And when the quantity of arsenic is very large the histo- 
logical elements are reduced to a state of impotence; they 
nourish themselves no longer, and phenomena result similar to 
those observed when an eschar is produced on the skin. 

Then, when you have caused them to perish, what will happen ? 
Phenomena due to consecutive alteration, to necrobiosis, will en- 



296 PRINCIPLES AND METHODS OF THERAPEUTICS. 

sue, exactly as if they had perished spontaneously (as for instance 
a tumor which becomes gangrenous) ; and in such a case, what 
will happen for the albuminoid matters contained in these tissues 
which have perished ? A fatty matter will be produced, which 
is the state of final decomposition of the histological elements, 
and which is produced also in dead bodies ; it is the fat of the 
cadaver. 

Steatosis ensues, then, in the various organs, that is, a fatty 
transformation, not to be confounded with the formation of fatty 
tissue. It is a fatty transformation of the parietes of the cells and 
of the histological elements in general. This steatosis is induced, 
then, in a certain number of cases of poisoning; but I have already 
shown you that when the dose of the poison is small the general 
symptoms observed have not the gravity which we here attribute 
to them. This visceral steatosis is, then, a phenomenon which may 
exist or may be wanting, even when the poison has caused death ; 
and there have been cases where death ensued and where no visceral 
steatosis was found at the autopsy. In certain cases where a 
moderate degree of steatosis of the liver (for it is this organ that is 
usually examined, this change being most marked in this gland), 
has been observed, it is necessary to be very reserved in con- 
sidering the signification of the post-mortem appearances. 

Have all the authors avoided the causes of misapprehension 
which deceive so many ? Have they a perfect knowledge of the 
normal state of the organ ? No : the greater number of those who 
thus examine organs post-mortem are ready to charge the poi- 
son with the production of any little peculiarity which they may 
find. 

This is what happened for Addison's disease; Addison 
himself described it as an affection characterized by indigestion, 
feebleness, cachexia, with a bronzed tinge of the skin ; and the 
suprarenal capsules are found, under such conditions, in a morbid 
state; the first phenomena, those of cachexia, etc., are the effects, 
the state of these capsules the cause ! But since his time the 
idea has been pushed further, and it has been said that a bronzed 
coloration of the skin is always accompanied by lesions of these 



ARSENIC. 297 

capsules, and a number of cases confirming this assertion have 
been, put forward. In one such case I objected, "But these 
capsules that you show me are normal, they are found in just 
such a state in every individual over twenty years of age, and 
consequently they have no signification." The distinguished 
person to whom I made this objection had never thought of 
examining a normal suprarenal capsule. 

There is a published observation in existence in which it is 
said, " the capsule did not appear much altered, but with the 
microscope we have found a large proportion of fat." But it is 
always so, and there is so much fat that with these capsules a 
milky emulsion may be made. 

The cases in which it was thought a pathological con- 
dition of the liver existed where the parenchymatous cells wore 
found to contain a considerable proportion of fatty matters, were 
very often cases in which the liver was in an absolutely normal 
state. 

There has been a work written on the steatosis observed in 
obese women and in women in the puerperal state ; later on, the 
author was obliged to recognize that this was the normal state ; 
and if animals are killed during the period of digestion, you will 
always find the liver fatty. Consequently, if you have given 
them, no matter what poison, it is possible that, in sacrificing 
them, you will find in the liver the hepatic cells charged with 
fat. 

Consequently, when the liver alone is fatty, too much im- 
portance should not be attached to the fact. 

The steatosis may be met with not only in arsenical poisoning, 
but also in almost any case of poisoning ; while, on the contrary, 
it is not always present in cases of arsenical poison ing which 
have proven mortal, and may be met with in fatal cases prodiuvd 
by other poisons. 

The steatosis caused by phosphorus has been long known, 
and this condition was first observed in that form of poisoning; 
then arsenical steatosis was described, then that induced by mer- 
cury, etc. All these facts are true, but should be received with 



298 PRINCIPLES AND METHODS OF THERAPEUTICS. 

the reservation I have made above. More singular still, a 
high degree of visceral steatosis may be met with in poisoning 
from substances differing very much from these, as in poisoning 
by sulphuric acid, or by ammonia. 

Electro-negative bodies and electro-positive bodies cause stea- 
tosis in an equal degree ; and these facts are not isolated ; I have seen 
two cases. I have observed one case of poisoning by sulphuric acid, 
and one by ammonia, both followed by death, and in which visceral 
steatosis was found in both cases, as in poisoning by phosphorus. 
You can then very well see that it is necessary to change the in- 
terpretation of this steatosis occurring in the viscera. 

I had thought that steatosis, when caused by phosphorus, 
might result from the fact that under the influence of a state of 
denutrition, of regressive transformation, insufficient combustion 
or oxidation ensued in the tissues, and consequently an exag- 
gerated proportion of fat remained in them. 

But there is no necessity to call into play so remarkable a 
causation ; it may be said that steatosis is the result of the death 
of the histologic elements, determined by any poison, whatever 
may be its nature ; when the quantity of the noxious substance 
is enormous, capable of hindering or suppressing the functions 
of the organ, and has arrived in the parenchymatous tissues, 
there are cells which are killed, and these cells undergo re- 
gressive transformation, and consequently, fatty degeneration. 
This is the way this phenomenon should be understood. 

Now, we will consider in what situations and in what state 
arsenic is found in subjects poisoned with it. Several different 
cases may be distinguished. 

If the poison has been recently administered, it must be 
sought in the digestive organs, and there you will find it in several 
conditions. As the arsenious acid, which is oftenest employed, 
is not very soluble, some of it is found in the intestinal fluids. 
There is another portion adhering to the surface of the villi, to 
the valvulse conniventes, or more or less incrusted on the mucous 
membrane. Then there is a certain proportion which passes, 
after death, by imbibition, into the tissues of the intestine and 



AESENIC. 209 

into the neignooring organs. It is a purely physical imbibition. 
When poison has been administered some time before death, it 
has first been carried into the ante-hepatic portion of the vascular 
system; then it arrives in the liver, where it accumulates, for two 
reasons: in the first place it is carried there directly; in the 
second, after its diffusion throughout the system, it returns to 
the liver, because this gland is the eliminating organ for arsenic 
and the metals. 

M. Laborde has published interesting facts concerning poison- 
ing by arsenic; he has observed that, under its influence, the 
biliary secretion was exaggerated at the moment arsenic entered 
the liver. Even when it is diffused and has taken its place in the 
tissues, it is still by the liver that it is partly eliminated. 

But when the symptoms have been prolonged, when the quan- 
tity of arsenic has been considerable, I said to you that it was 
necessary also to seek it in the tissues themselves, and not only 
in those bathed in the blood, not only in the nervous system, 
but also, and particularly when the poisoning dates far back, in 
the caducous organs, in the hair. I do not doubt but that it 
may be found in the nails, which is one way by which the 
metals are eliminated. Thus I have remarked a brownish 
tinge of the nails in healthy subjects who take sulphurous baths. 
This shows that in the nails there is a certain proportion of iron 
in the normal state. It is for the same reason, when patients in 
lead poisoning have taken a large number of sulphurous baths, 
that you will finally notice after a bath that the base of the nail, 
which is impregnated with the lead, becomes colored. 

I said that it was in the interior organs that arsenic should be 
searched for, particularly in the elements of the nervous system ; 
but the osseous tissues must also be examined, since there we 
have an entire system where arseniate of lime may take the place 
of phosphate of lime. 

It is, then, in the hair and in the bones, when the subject 1 in- 
been long dead, that arsenic must be sought for, with this condi- 
tion, however, that large doses have been originally given. 
Moderate doses, which have been administered during a short 



300 PRINCIPLES AND METHODS OF THERAPEUTICS. 

space of time only, may produce the most grave functional dis- 
orders, and may even cause death without leaving durable traces ; 
for never, at any moment, has there been a sufficient excess of 
arsenic that a part might be left to constitute an integral part of 
the histological elements. The liver and the other emunctories 
will have had sufficient time to eliminate the uoisou, so that it 
will be impossible to find any trace. 

This permits us, at present, to understand how death is pro- 
duced through the influence of arsenic ; it is necessary to distin- 
guish between the different forms of poisoning, and if this 
distinction (with careful discrimination) is not made, you will not 
properly understand the facts presented to you ; you may not 
only deceive yourself, but deceive also the public authorities who 
may apply to you. Distinction must be made between three 
different forms of poisoning. 

In one set of cases an enormous quantity of arsenic is given at 
one time ; this poisoning is done by unskillful persons who have 
just entered on the business, and who give frightful doses to 
those they wish to rid themselves of. Two things may happen. 
Either the subject recovers, notwithstanding the largeness of the 
dose, just as happened for the woman of whom I have spoken, 
or he succumbs; and if he dies, it may be with simply choleriform 
symptoms, exactly as if any other caustic had been introduced 
into the digestive tube ; that is to say, there are not only phenom- 
ena due to local irritation, but also the reflex and sympathetic 
phenomena which characterize the choleriform state ; the indi- 
vidual may die as if struck by lightning, or he may succumb to 
the local lesions, or to the reflex phenomena which they induce. 
But he may also die through all the series of phenomena super- 
vening on the diffusion of the poison throughout the system, and 
of which I have shown you the exaggeration under the influence 
of massive doses. 

Such, then, is the first form of poisoning by arsenic by massive 
doses. As relates to the other forms, I will speak to you in 
the next chapter. 



AESENIC. 301 



CHAPTER XXIV. 
Arsenic (Continued). 

Albuminuria, its interpretation. Concerning death by arsenic (continued). 
Importance of taking into consideration the difference in doses. Modes 
of poisoning by arsenic. 



Gentlemen : 

Before going further, and before speaking of the two other 
forms of fatal poisoning by arsenic, I wish to speak to you of a 
symptom which hitherto has not been well explained ; it is the 
occurrence of albuminuria. 

A certain number of cases of albuminuria have been consid- 
ered due to the passage of the arsenic through the kidneys. But 
this is a faulty interpretation, which has been applied, also, to 
poisoning by lead and by mercury, and which provokes criticism 
in these two cases, just as when applied to arsenic. And the 
proof that the passage of lead or mercury is not the habitual 
cause, or worthy of attracting attention, is the fact that in a gnat 
number of cases, where the poison is in considerable quantity 
and has been rapidly ingested, albuminuria is not present. 

Albuminuria supervenes in the period of cachexia, and is thus 
observed ordinarily in chronic lead poisoning. You will see 
individuals arriving from the white lead factories at Clichy pre- 
senting very grave symptoms of lead poisoning, but you will 
not find a trace of albumen in their urine. But if in the end 
they fall into a cachectic state, which, in such a case, will be 
saturnine cachexia, they will have albumen in the urine, and this 
will continue to be present even when the poison lias been com- 
pletely eliminated from the system. Another proof is this foot, 
first indicated by Overbeck, in poisoning by mercury. Albu- 



302 PRINCIPLES AND METHODS OF THERAPEUTICS. 

minima, at first present, disappears later, to reappear at a certain 
period through the influence of a cachectic state. 

At a certain period of the affection Overbeck administers 
iodide of potassium, to rid the system of the poison, which then 
reappears in the urine, and at this moment albumen is no longer 
found. 

I have observed the same fact in the case of which I have 
several times spoken. Albuminuria was present, but disappeared 
the moment that I caused a considerable quantity of arsenic to 
reenter the circulation. Consequently, the albuminuria observed 
in cases of poisoning must not be considered as produced entirely 
by an exaggerated state of irritation at the moment the poison is 
eliminated from the body in the urinary secretions. 

The albuminuria in such cases is but the expression of the 
general state of the system ; the dyscrasia shows itself, as I have 
often demonstrated, by the presence of albumen in the urine. 

We have briefly considered, in the last lecture, the different 
forms of death after arsenical poisoning, but I have not ex- 
plained to you the manner of dying when variable doses of 
arsenic have been employed. This we will now consider. 

When the doses are moderate or small, but sufficient, how- 
ever, to produce certain effects, then the disorders are much more 
obscure than when massive doses have been taken ; the symptoms 
almost all point to the digestive tube ; but the effects produced 
are none the less dangerous, and death, even, may ensue when 
the doses have been repeated a sufficient length of time. The 
first mode of poisoning (by massive doses) corresponds to what I 
have called poisoning by unskillful, inexperienced hands. This 
second mode will be observed after poisoning by pretty strong 
doses, repeated for a period of time. 

But the symptoms of this second form may also be observed 
when pretty large doses of arsenic have been administered thera- 
peutically, and it is necessary that you should be acquainted with 
the possibility of its occurrence under such conditions. 

There is a third form of poisoning, which we must stop an 
instant to consider. It is that which is executed by skilled 



ARSENIC. 303 

hands, and is produced by small doses. Small doses ? It is 
necessary to understand what is meant by small doses. There 
are no doses absolutely small, and none absolutely large ; for I 
have shown you that the proper dose varies, according to the 
general state of the system at the time. 

Suppose, for instance, that the dose may be two, three, four 
or even five centigrams per diem. I say that such a manner of 
proceeding is of incalculable advantage to the criminal who puts 
such a plan in execution, and you will easily understand why. 

In the first place, with doses comparatively small the symp- 
toms observed are of a less serious nature ; you will never observe 
the terrible effects produced by massive doses. There is no 
question of choleriform symptoms. You will have simply symp- 
toms of trouble in the digestive organs, nausea, vomiting, loss 
of appetite, followed by diarrhoea, to sum up : all the phenomena 
observed in a large number of affections occurring spontaneously 
or produced by causes differing widely from the ingestion of 
poison. Such phenomena are observed in dyspepsia and in diar- 
rhoea, or are produced by cold, by heat, by humidity, or through 
indigestion. Thus you have symptoms much milder than 
usual, and which, again, have no very evident signification, and 
therefore do not attract attention sufficiently to cause suspicion. 
This state continues, and little by little the digestive functions 
become more difficult of performance ; the diarrhoea seems to 
become constant. But an end is put to all these symptoms ; 
from time to time the medicament is suspended, the thread of 
life is not severed all of a sudden, and all the dangerous 
symptoms disappear. There is a sort of amelioration, which 
lasts for a variable time ; nevertheless, little by little the pheno- 
mena due to the breaking up of the constitution return; there is 
a general diminution of strength throughout the system ; there 
is anaemia — everybody speaks of anaemia ; it is seen everywhere. 
Consequently, when a person suffers from troubles in the digestive 
organs, when there are also nervous troubles, it is thought that 
all is clear ; for nothing is more frequent than to observe nervous 
symptoms accompanying anaemia. 



304 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Again, another series of advantages: the poison is present 
always in small quantity, and it becomes difficult to demonstrate 
its presence in any considerable quantity to satisfy the scruples 
of those who are doubtful of its existence ; even when death has 
been produced and when the poison has not been eliminated, this 
difficulty would still exist. 

But when care has been taken, besides, to suspend from time 
to time the administration of the poison, when, consequently, there 
has been time for elimination, the proof of guilt is in part want- 
ing, and does not exist in all parts of the system, as is generally 
thought; for it is generally imagined that in cases of poisoning 
the substance which causes death can be found in all parts of 
the organism. Under the conditions I have specified, it is not 
so ; not only the poison has been in part eliminated, but the little 
that remains is not diffused throughout the system ; sometimes it 
has not gone further than the liver. It remains fixed in this 
organ, and on examination no noxious principle is found in the 
elements of the tissues where it is habitually deposited. Conse- 
quently, after an official autopsy has been made, its presence 
cannot be demonstrated, either in the bones, or in the brain, or in 
the hair. 

With even more reason, then, under such conditions, no grave 
symptoms are observed; nor any functional disorders which 
would be without organic lesions if they were present ; there is 
no paralysis before the patient succumbs, and when he does suc- 
cumb, no steatosis is found. Steatosis may be wanting when the 
doses have been excessive, but it is never found except when they 
have been so. 

You see what obstacles are accumulated in the path of experts 
in medical jurisprudence, and how difficult it is for them to de- 
monstrate that poisoning has taken place. They cannot bring 
forward any very significant fact, they cannot demonstrate the 
presence of arsenic in the brain, they cannot produce any con- 
siderable quantity of the poison; the entire demonstration is evi- 
dently incomplete. 

Notwithstanding all these difficulties, you will soon see that 



AESENIC. 305 

it is possible to arrive at a demonstration of the presence of 
poison. 

But, first, we should consider whether it is really true that two 
or three centigrams of arsenic per diem may in the end produce 
death? There are, as I have told you, individuals who eat 
arsenic, and others who, without having thus acquired compara- 
tive immunity, resist it for a period. 

Arsenic should not be considered merely a corrosive poison, 
acting only by the grave lesions it produces, exciting more or 
less active inflammation, with eschars and all the lesions that en- 
sue, as when a piece of caustic potash or a considerable dose of 
chromic acid falls into the stomach. It is not thus that it acts; 
or, at least, if it acts thus, it has also other effects, resembling 
those produced by emeto-cathartics. 

Arsenic exercises a poisonous influence on the digestive tube, 
even when no appreciable irritation has been caused; it induces 
nausea, just like tartar emetic, like sulphate of zinc, and like 
sulphate of copper, that is to say, in virtue of a property, special 
to it, if you wish, but which belongs also to a group of bodies, it 
determines an effect on the peripheric end of the pneumogastric, 
which is shown by the existence of nausea. 

Can emetin and substances of analogous action be considered 
escharotic? No; they are substances which have a peculiar 
action on the form of sensibility found in the stomach and digest- 
ive tube. This will make us understand why it is not necessary 
to introduce large doses of arsenic to produce its nauseating effects, 
no more necessary than to introduce large doses of sulphate of 
copper. Twenty centigrams and often even seventy centigrams 
will be sufficient. 

It may be mentioned, in passing, that there is another error 
which is becoming prevalent, that is, that the salts of copper are 
incapable of causing poisoning. I do not pretend to say that the 
noxious effects of these salts have not been exaggerated, that they 
have not been considered more poisonous than they really arc; 
but to say that they are absolutely free from poisonous proper- 
ties, is to place one's self in flagrant contradiction with the facta 



306 PRINCIPLES AND METHODS OF THERAPEUTICS. 

observed, and ignore what is at present known concerning the 
drug. 

If copper is introduced in very small doses, so as not to pro- 
duce any effect on the digestive organs, it may thus enter into the 
general circulation and be eliminated continually as it is intro- 
duced, without provoking any grave symptoms. But if the dose 
is sufficiently large to provoke nausea and vomiting, with all the 
phenomena observed in such a case, and if these symptoms 
reappear each day, then you may see the subjects fall into the 
cachectic state observed when smaller doses of arsenic — for this 
poison possesses greater energy — -have been administered. But, in 
reality, the mechanism by which the lesions are produced and 
the co-existent phenomena, are similar. 

I will now attempt to show you in what manner arsenic in 
single doses, producing this nauseating emeto-cathartic action, 
may nevertheless, when administered in repeated doses, deter- 
mine the injurious effects with which you are already acquainted, 
which have been indicated in judicial cases, and which may 
even cause death. 

A substance capable of inducing emeto-catharsis produces an 
exaggerated gastro-intestinal secretion, which is not simply 
mucus, but contains also so large a quantity of albuminous 
serosity that if treated by heat or the acids it coagulates. 

There is, then, spoliation of the system ; it is as if a serous 
bleeding was repeated at short intervals. 

When vomiting is produced it is an action which requires 
considerable effort of all the powers of expiration, and conse- 
quently there results a loss of strength. As proof of this it 
is sufficient to notice the state of prostration into which an 
individual who has just vomited is thrown. 

Consequently, as we have seen, there is a loss of strength 
through vomiting ; and even oftener, through emeto-catharsis, 
are observed those phenomena, due to the reflex sympathy excited 
in the general system, which accompany abdominal diseases and 
are en rapport with the obstacle existing to the performance of 
the functions of the sympathetic nerve. 



ARSENIC. , 307 

These phenomena merit the name of peritonism, or of cholcri- 
form affections, which I have given them. You are all ac- 
quainted with the form of cholera produced by tartar emetic, 
which may be induced by iive centigrams of the drug, and 
which, when death ensues, may leave but a slight reduess, with- 
out any veritable inflammation determined by the noxious 
substance. 

What really happens when this choleriform state is observed ? 
There is extreme prostration ; great disorder in the performance 
of the various functions ; hsematosis is hindered, the circulation 
languid ; the pulse is small and becomes very slow or excessively 
rapid. If the combustion is suppressed or becomes less active, 
what happens ? The rehabilitation of the tissues becomes im- 
possible ; there is no reparation of the losses undergone by the 
organism, and consequently there are languidness and impossi- 
bility of general nutrition, caused by the suppression of the 
gastric functions, or at least by the diminution in the functional 
activity of the stomach. Consequently, as you see, many 
obstacles are placed in the way of the performance of the various 
functions, and in the way of general nutrition of the system. 
And if these obstacles continue to exist, if, instead of lasting for 
days, they are present for weeks, you can understand what will 
ensue : losses which cannot be repaired ; insufficient nutrition ; 
consequently, little by little, organic decadence, marasmus, and 
death. 

I do not pretend that the small doses of which I have spoken 
suffice to kill everybody; I am of opinion that many among you 
would survive such doses, because you are possessed of that vital 
resistance which will enable you to surmount many obstacles in 
life. 

But suppose a puny creature, with a shattered constitution ; 
suppose that this being has already suffered from lesions more 
or less serious in the digestive organs; you will see produced 
from small doses grave symptoms which may have the fatal 
character with which I have just endowed them. 

This is so true, that when you employ arsenic in therapeutical 



308 PKINCIPLES AND METHODS OF THEKAPEUTTCS. 

doses, it will happen to you to meet with cases in which the di- 
gestive organs are of extreme sensibility, and where arsenic will 
cause symptoms more or less serious. 

This is remarked frequently by practitioners who employ 
arsenic against intermittent fever ; they administer two or three 
centigrams from the beginning, Boudin even giving five centi- 
grams; and it happens that in a certain number of cases these 
doses cause vomiting, diarrhoea, and symptoms of collapse, due 
to the sympathetic effects which characterize any lesion or affec- 
tion of the sympathetic nerve. You find yourself then obliged 
to cease the treatment by this drug. 

When you meet with such individuals, it is clear that if you 
persist in the use of the drug, you may in the end determine grave 
symptoms. And when these symptoms, which, if they lasted but 
one day, would not be a source of great danger, are continued for 
a considerable time, there ensues in the end that diminution 
of strength, that alteration of nutrition, in one word, that state 
of cachexia, which may very readily terminate by causing death. 
It will suffice to breathe, if it may be so expressed, on this shat- 
tered organism, to bring about irremediable injury. 

Here a question presents itself for consideration which might 
have been taken up when speaking of the occurrence which 
gave occasion to this discussion. It is to know of what nature 
may be this last breath, or act, which may extinguish an 
existence so deeply shattered. It may be almost anything; 
perhaps a last dose of the poison, or a trifling intercurrent 
malady. The patient is already very much shattered ; he takes 
cold, suffers from fever, he sinks, and the little that remains of 
life is extinguished. 

There is another circumstance meriting attention; it is the pos- 
sibility that the poisoning has been repeated several times. I 
have heard a magistrate say that criminals themselves generally 
point out the way to follow in order to discover the particu- 
lars of the crime ; no matter how well prepared to keep silent, 
they allow to leak out, in the end, something concerning the 
subject which fills their thoughts, as robbers, according to what 






AESENIC. 309 

detectives say, always turn at street corners, to assure themselves 
that they are not pursued. 

In a recent trial, the accused said, " I do not know but that, 
by chance, belladonna may have been taken." It is to be re- 
gretted that this clue was not followed up. It is certain that 
sometimes even a quite medium dose of a vegetable poison, 
always difficult to detect, suffices to destroy life. It is the more 
difficult to recognize its presence since it will come in contact, in 
the digestive tube, with elements of destruction, acids, alkalies, 
substances in a state of fermentation, the ferments normally 
present, as pepsin, diastase, pancreatin, and ferments accidentally 
present, which exist everywhere, by virtue of the law of pansper- 
mism, with which you are all acquainted. 

Consequently, you see how easy it is to understand how death 
may occur even in cases where the symptoms of poisoning have 
remitted, from time to time, in intensity, and where the doses 
have been moderate. It suffices that the system of the individual, 
in these cases of intermittent poisoning, be predisposed ; that 
there be great susceptibility of the digestive organs, with great 
constitutional feebleness. Great attention must, then, always be 
paid to the state of the system of the individual who has been 
poisoned. 

We can, then, at present, understand the extreme diversity in 
different cases, the resistance presented by one subject or the fra- 
gility of another. Some resist the most violent, the largest, most 
massive doses — this woman, of whom I have spoken, recovered 
after taking eight drachms, at least, of arsenious acid — while 
others succumb under the least pretext, if I may use the expres- 
sion ; so that the minimum fatal dose may be twelve, even ten 
centigrams; and, on the other side, the maximum tolerated may 
reach as high as eight or ten grams; thus differing in the pro- 
portion of one to ninety, or even one hundred. 

What is the explanation of this difference ? It is found in 
the constitutional state of the different individuals, as I am about 
to indicate to you. There is extreme diversity as regards the 
susceptibility to impressions of the digestive organs } a- regards 



310 PRINCIPLES AND METHODS OF THERAPEUTICS. 

the receptivity of the entire system for the poison, and as regards 
the facility of elimination. 

If you suppose an extreme tolerance for arsenic on the part of 
the stomach and intestines, you will not witness the production 
of any of those local disorders which you have just seen to pro- 
duce death. You will not observe any symptoms in the mucous 
membrane of the intestines, nor any appearance of sympathetic or 
reflex phenomena. If, at the same time, the activity of nutrition 
and absorption in the tissues is very marked, the poison will not 
be deposited. 

When a subject is young his tissues are rapidly renewed ; 
nothing remains long unchanged in him. Under such condi- 
tions there will be less accumulation in the parenchyma of the 
different organs and in the tissues of the nervous system than 
under contrary conditions. You are, then, yourselves, under 
favorable conditions. But when with this the kidneys are 
largely open, when the urinary secretion is abundant, and con- 
sequently the arsenic ingested can freely pass out of the system 
by this open way, it is clear that this individual, whose digestive 
organs tolerate so well the irritation produced by the poison, in 
whom nutrition is so well accomplished and the bile so freely 
formed and secreted, can ingest moderate and even strong doses 
without the production of perceptible symptoms. This subject 
will be one of those who resist even massive doses of arsenious 
acid. I do not say that such resistance is not an exceptional 
fact ; but it happens. 

Suppose contrary conditions — digestive organs exceedingly 
susceptible to impressions, which nevertheless, through feebleness 
of the various functions, cannot disembarrass themselves of the 
poison which injures them; nausea, prostration, exhaustion, col- 
lapse will be observed. Again, the general condition of the 
system is bad ; advanced age, constitutional state, all will tell ; 
organic renewal is slowly brought about ; the " nutritive whirl- 
wind " of Descartes has become slower. Suppose that in this 
same subject the secretions are not at all abundant, the skin does 
not well perform its functions, the liver secretes little, the urine 



AESENIC. 311 

is scanty. Under these conditions doses relatively small will 
remain, will be delayed, finally will accumulate in the tissues, 
and in the end will determine not only local but also general 
symptoms; not alone a species of intermittent poisoning, but 
generalized arsenicism through diffusion of the poison. In many 
cases, under such conditions, all that will be observed are the 
symptoms induced by the local effect of the poison and through 
sympathy, and which are symptoms always accompanying ar- 
senical poisoning. 

Your opinions on this subject should, then, be fixed, as it 
seems to me. I have exaggerated nothing ; I have shown you, 
in good faith, the effects produced by arsenic, as I understand 
them, and as I have observed them in a large number of cases. 

Now we can approach the consideration of a question which, 
though of a somewhat different nature, is none the less inter- 
esting from a medico-legal point of view. It is not sufficient to 
know that the facts are as above presented ; it is also necessary 
to know how to recognize a case of arsenical poisoning. 

I will commence by a declaration which should head all 
discussions on diagnosis ; that is, that there does not exist any 
one fixed pathognomonic symptom which must necessarily be 
present. 

The existence of pathognomonic symptoms has long been 
believed ; the lenticular, rose-colored spots were considered an 
evident sign of typhoid fever, and opinions on their nature have, 
varied with the denominations of the disease ; to-day we know 
that these spots may be wanting in typhoid fever and may exist 
in other affections, and particularly in acute miliary tuberculosis. 
These signs have long been believed in, the more so because 
specific causes and something special about disease in general 
were believed in. 

A return was unwittingly made to the doctrines of the middle 
ages when cancer was considered to be a parasite which devoured 
the tissues; and so much faith was put in this interpretation that 
fresh meat was used to turn aside its action from the tissues. 

It is the same thing when it has been asserted that there exist 



312 PRINCIPLES AND METHODS OF THERAPEUTICS. 

characteristic cells in each species of tumors. Always the same 
error, sometimes gross and apparent, again hidden under scien- 
tific expressions. I will add that there is no absolutely necessary 
symptom in the history of any disease. This declaration made, 
it remains but to say, to complete it, that the diagnosis of a 
malady is made, not by one or two symptoms, but by the 
ensemble of symptoms. It is not only necessary to have all the 
symptoms present, but the malady must develop itself in the 
usual way, the symptoms occurring in determined order. So 
much so that you may in different maladies have the same set 
of symptoms, but occurring in a different order. 

For instance, typhoid fever, has the following evolution: 
headache, fever, the patient takes to the bed, diarrhoea follows 
and remains the predominant symptom. Take cholera, on the 
other hand, and the choleriform affections; in these you remark 
the same symptoms, if you take them one by one : very intense 
fever, grave intestinal lesions, headache. What is the difference? 
The symptoms are the same, but their evolution is different. If 
the patient syas that in the commencement he had great aqueous 
diarrhoea, that this diarrhoea has little by little become less 
marked, that the fever, at first imperceptible, has become intense 
and reduced the subject to the state in which you find him, then 
you will consider that it is a case of choleriform diarrhoea with 
consecutive fever, induced by reaction. The other patient, in 
whom the d6but of the affection was slow and without prominent 
symptom, the diarrhoea gradually increasing, will cause you to 
think of typhoid fever. Apply this mode of reasoning to 
arsenic poisoning as to every other affection. 

It is by the peculiar course of the affection, notwithstanding 
the absence of a certain number of grave symptoms, that you 
will in the greater number of cases recognize its nature. 
Exactly as if you detach a stone from one of the towers of 
Notre-Dame, even from one of the angles, there would be no 
difficulty on that account in recognizing the tower. Even if 
several stones were removed there would be no difficulty in 
recognizing it. 



ARSENIC. 313 

It is just the same with a symptomatic series ; if a part is 
wanting you will still be able to recognize the malady. The 
most special phenomena of the disease may disappear, one by 
one, or even by groups, without hindering its recognition. 
For instance, in arsenical poisoning the burning sensation in 
the throat may be absent. It suffices, to prevent its appearance, 
that the poison be given in pill instead of in a liquid form ; and 
nevertheless, this symptom seemed so characteristic that in the 
late case it was considered necessary to have demonstrated that 
the patient suffered from burning in the throat and from thirst ; 
that is, to show the existence of a contingent symptom, arising 
from the topical action of the poison at the entrance of the 
respiratory organs. 



314 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XXV. 
Arsenic ( Continued) . 

Diagnosis of poisoning ; difficulties encountered ; no pathognomonic symp 
toms ; medico- legal considerations. Imbibition by certain substances ; 
histologic deposits. 



Gentlemen : 

I demonstrated to you, in the last chapter, taking arsenic as 
an example, how little dependence could be placed on one or two 
symptoms, even though reputed characteristic ; and I said to 
you, in concluding, that the much talked of burning in the throat, 
on which legal authorities have so much insisted, may be wanting 
and is wanting in all cases where the poison has been directly 
introduced into the stomach, without having come in contact with 
the throat. 

It is the same for cutaneous eruptions; in this case they 
wished to find them, as if such eruptions were not wanting in the 
great proportion of cases, their presence being due to topical 
action, to the effects produced by arsenic in fine dust impregnat- 
ing the skin. On the contrary, the proper arsenical lesions are 
due to the passage of the poison by the cutaneous emunctories, 
and are wanting in a great number of cases. You see, then, 
what dependence can be placed on the occurrence of this symptom. 

Consider the nervous symptoms; in almost every case of arseni- 
cal poisoning these are observed, yet paralysis* is of so excep- 
tional occurrence that certain authors even deny its existence. 
The existence of arsenical paralysis cannot be doubted ; but it 
is not of common occurrence; consequently, you have not the 
right to demand its presence in order to fully prove that poisoning 
by arsenic has taken place. 



ARSENIC. 315 

I may say the same of steatosis ; it is characteristic of poison- 
ing by very large doses, and it may not be produced even with 
such doses, since in the case I have so often mentioned recovery 
took place ; and certainly the existence of fatty degeneration of 
the different organs is incompatible with the continuation of 
life. 

Consequently, as you see, here are quite a number of symptoms 
reputed characteristic, and which not only may be wanting, but 
which, to a certain extent, should be wanting in many cases. 
On the contrary, these same symptoms may be met with in 
other affections; this burning sensation in the throat — all the 
acrid poisons determine it ; poisoning by ammonia is accompa- 
nied by a horrible sensation of burning heat, of veritable scalding 
in the throat, and excites unextinguishable thirst, more peremp- 
tory than if the subject had been poisoned by arsenic. 

The vomiting and gastro-intestinal symptoms capable of taking 
a choleriform aspect are observed as well after poisoning by 
metallic substances, such as sulphate of copper, or of zinc, as after 
arsenic has been taken. 

This series of grave symptoms, due to the impression made on 
the abdominal portion of the sympathetic nerve, are observed in 
all cases of poisoning, even by moderate doses, or during a time 
when choleriform diarrhoea is prevalent; they have been ob- 
served when only five centigrams of tartar emetic had been 
taken. 

The paralysis, when it exists, is certainly of a peculiar type ; 
but would you be willing to conclude from this that you have 
before you a case of arsenical poisoning, when you have also an 
identical form of paralysis in lead poisoning and in that pro- 
duced by mercury ? 

I have shown you an example where the great authority of 
Duchenne corroborated what I have said ; it is a symptom which 
may be observed after poisoning by any substance, but particu- 
larly in poisoning produced by lead, ammonia, and sulphuric 
acid. Consequently, you can see that paralysis is a symptom of 
slight value as regards the diagnosis of the case, 



316 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Will you then conclude that the diagnosis is impossible ? That 
because certain significant phenomena are wanting, because cer- 
tain symptoms may be observed in any case of poisoning, that all 
means of diagnosis are wanting ? No ; diagnosis is not impos- 
sible; but it is necessary to have present a certain ensemble 
of symptoms, undergoing evolution in a certain determined order, 
and the conditions under which they are observed must be taken 
into consideration. 

What is observed in the great majority of cases are the gastro- 
intestinal phenomena, common to most cases of poisoning, but 
which acquire value through the conditions under which they 
may be observed; vomiting, or at least nausea, may be present; 
atonic dyspepsia with catarrh, or true diarrhoea, prostration of 
strength, and then certain co-existent phenomena ; slight frigidity, 
a more or less notable diminution in the force of the cardiac pul- 
sations, in a word, all the adynamic symptoms which accompany 
diseases of the digestive organs. I repeat it, these symptoms are 
observed in cases of poisoning by different substances. But when 
the symptoms persist, or intermit from time to time, always under 
the same conditions, and if there is an interval of complete rest 
under such conditions, and in the absence of the ordinary causes 
which give rise to such phenomena, you will find yourself under 
the obligation of considering if there may not be some outside 
artificial cause intervening to produce the symptoms observed. 
When you observe these symptoms supervene, you are obliged to 
take into consideration the very grave hypothesis of poisoning. 
This is what happens in a certain number of cases, and notably 
in the recent affair which has caused this digression. 

This supposition will acquire still more importance when death 
ensues, and the physicians, who, during life, had not been able 
to determine any cause capable of producing the symptoms ob- 
served, cannot, even at the autopsy, find any of the lesions which 
habitually determine gastro-intestinal disorders. During life it 
may have been thought that an ulcus rotundum existed, that a 
true inflammation, or tuberculous lesions, or advanced anatomical 
changes in some organ, would give the explanation of the serious 



ARSENIC. PA 7 

symptoms. But no ; the autopsy shows no anatomical lesion. 
When this is the case, what before was but supposition becomes 
a probability. 

If it be added that the organs which necessarily would come 
in contact with the arsenic, and come under the influence of its 
antiseptic properties, are in a state of perfect preservation, as if 
death had just before taken place ; if the stomach preserves its 
greyish-rose tint, if the intestine has its normal coloration ; if all 
this is the case, then the presumption that poisoning has occurred 
becomes of extreme probability. 

But the observations of the physicians alone will be insuffi- 
cient. The chemist makes his examination and reports ; yes ; in 
these organs, which have seemed to enjoy almost entire immunity 
from putrefaction, notwithstanding the period of time since death 
took place, in these organs I find arsenic, in very notable propor- 
tion, and I present you with capsules covered with spots. 

Do you not find that under such conditions the presumption 
of poisoning may be considered as proven ? 

And if in conjunction with this, none of the grave lesions 
possible of production in the organs observed can have inter- 
vened to induce the symptoms observed during life j if the topo- 
graphical distribution of the arsenic is taken into account, it being 
found in the intestine and in small proportion in the liver, but 
not in the other organs, the presumption of poisoning becomes 
almost a certitude. 

But when the life of a human being is in the scale, almost a 
certitude is not sufficient j absolute certainty of the fact is re- 
quired. 

And in that the duty of the expert differs widely from that 
of a member of the jury; the latter has the right to have his 
private impressions regarding the case, to judge it somewhat 
through intuition; he allows himself to be guided by the moral 
and physical aspects of the facts. 

The expert has no right to intuitive opinions, and can allow 
himself to be guided solely by the i\wt* from which he draws 
conclusions. A private opinion should never take the place, 



318 PRINCIPLES AND METHODS OF THERAPEUTICS. 

for him, of scientific conviction. On this account I said, in a 
recent trial, poisoning has, in all probability, taken place. But 
if I had been a member of the jury I should have voted yes. 
At present we may pass in review the different objections made 
against this interpretation of the facts in that case. 

The two experts, both men of probity, both convinced, agreed 
in saying : " There is a certain proportion of arsenic present (this 
was difficult to deny,\ for arsenical spots on porcelain were shown), 
but it is not in sufficient quantity." 

How ? There is not enough ! But there is always too much ! 
Should any be present in the normal state ? I very well know 
that Raspail, who in a certain trial sought to terrify the judges, 
said : " But, Monsieur le President, I consider it possible for 
me to demonstrate the presence of arsenic even in your arm- 
chair." Such an assertion does not even merit serious attention. 

Without doubt arsenic is present in many substances — in can- 
dies, in artificial flowers, which are much less worn than formerly, 
but it is not so widely disseminated as has been pretended. The 
much talked of curtains containing arsenic were cited, but the 
lining did not contain any, consequently they could not have 
caused the poisoning of the patient. But arsenic was found 
where it should not have existed. A short time ago I was speak- 
ing with M. Th6nard, who, as a chemist, had followed the trial. 
He said to me: "Your reserve was much to be praised; but to 
me the culpability of the accused was evident ; even if there had 
been nothing but the facts brought forward by the experts and 
not contested, except as to their interpretation, there was suffi- 
cient proof." 

Yes, it ■ is evident that sufficient proof existed, for if we go 
back to historical cases where poisoning certainly occurred, 
and in which the proportion of arsenic present was determined, 
we see that in a certain number of cases there was no more, 
and sometimes even less, than has been shown to exist in this 
case. 

Thus, in the Lefarge case there was no more than a milligram, 
or even half a milligram, found and extracted, while in this case 



ARSENIC. 319 

M. Lhote considered it possible to find, in the whole digestive 
tube, four milligrams. 

You can then see that even considering the history of arsenical 
poisoning, the quantity found was sufficient to demonstrate the 
reality of the poisoning. Another argument brought forward 
was that no arsenic was searched for in the brain* I have, in 
advance, put you on your guard against exaggeration of the value 
of this argument. I have shown you that in poisoning by small 
or minimum doses, which, during a certain time are no longer 
given, the poison enters but a certain part of the organism; it 
arrives in the liver, in the large gland which arrests mineral 
substances, and if it passes into the circulation the proportion is 
small, and elimination taking place, but an infinitesimal part 
remains in the substance of the different organs, and in the tissues 
of the nervous system in particular. 

Consequently, there was no necessity, in this case, to demon- 
strate the presence of arsenic in the brain. Other arguments were 
made, and I wish to pass them in review, because at the moment 
they were presented I felt an intense desire — which I resisted, 
and I think properly — to take up these arguments one by one, 
and — I don't fear to say it — demonstrate their complete fallacy. 

I did not do so, and for the following reason : I had formed 
a personal opinion, and I determined to maintain it, to the 
effect that poisoning had in all probability taken place. And 
if I had entered into a discussion I might have allowed it to 
be seen that, in my private opinion, it was certain. This I did 
not wish, for I was an expert and not advocate. Here are the 
series of arguments invoked : First, it was said, and it was the 
feeblest argument, "There is a charge of arsenical poisoning 
This is astonishing! I am acquainted with two forms of 
arsenical poisoning, which have been well described, and try as 
I may, I cannot reconcile the picture presented of this case with 
either of the forms with which I am acquainted." 

It is just as if one said : Typhoid fever? But there are only 
two forms, ataxic and adynamic. The reply is: in a disease 
of this kind there are as many forms as there arc patients ; it is 



320 PRINCIPLES AND METHODS OF THERAPEUTICS. 

by mental effort and study that these two forms have been sepa- 
rated from the others ; but besides them do we not find other 
forms? Do these two forms include the slow, nervous form, 
etc.? In the same order of argument is the absence of the peculiar 
Hippocratic countenance, with sunken eyes. This appearance is 
noted only in certain forms, and as well when tartar emetic has 
been used as with arsenic, and occurs when the dose is large and 
the lesions of intense gravity ; otherwise it does not exist. But 
I will not insist on such an argument. 

But, again, here is a series of arguments which appeared to 
make considerable impression — I will not say on the jury, who 
did not appear to understand their value — but on the public at 
large. First, it was said certain omissions occurred in the 
examination ; thus, the presence of arsenic was not searched for 
in the brain. I have already shown what should be thought of this 
circumstance. But, again, the meningeal membranes were not 
examined to determine if tuberculous granulations existed, and 
if granulations were there present all would be explained. 

Is it possible, I would ask, that a physician be so unacquainted 
with the course of disease as to confound the symptoms of tuber- 
culous meningitis with gastro-intestinal disorder, characterized 
by vomiting and diarrhoea, with absolute integrity of the intel- 
lectual functions, and the absence of any symptom of lesion of 
the nervous centres ? Can it be admitted that such lesion would 
have explained all ? It was said, also, that if steatosis of the 
kidneys was found all would have been explained ; that the 
lesion of the kidney might have been accompanied by uraemia, 
which would have accounted for all the symptoms. 

I am not acquainted with any form of uraemia — and I have 
devoted much attention to albuminuria — which presents this abso- 
lute intermittence in the symptoms. I do not know any form 
which has an exclusively gastro-intestinal character, without 
ever presenting symptoms pointing to the nervous centres. 
I am unacquainted with any form of uraemia existing inde- 
pendently of the other classic phenomena of albuminuria, such 
as oedema, etc. Consequently, I do not believe that uraemia, in 



ARSENIC. 321 

any case, could explain the phenomena which were observed in 
this case of poisoning. 

It was a matter of regret, also, that the large intestine had not 
been examined, because, said the author of this remark, the 
woman had suffered from typhoid fever, and we know that in 
typhoid fever the lesions are found in the large intestine. If a 
hospital externe had said the same thing at a competitive exami- 
nation he would justly be rejected, as in typhoid fever it is the 
small intestine that is affected, and not the large. But the large 
intestine could be brought into argument, as only the small in- 
testine had been opened. No importance need, then, be attached 
to this argument. 

Then the condition called pernicious anaemia was brought into 
play. Ah ! pernicious anaemia . Most of you know what that 
means, although the affection is of recent creation. It is that 
state of profound, progressive anaemia which often, in effect, 
terminates by death, and which the physician cannot understand. 
It might be called perfidious, rather than pernicious. It places 
the physician in an uncomfortable position. Better informed 
practitioners generally perceive, or at least, suspect the cause, 
and the number of cases where this cause has been deter- 
mined and proven is sufficiently considerable to demonstrate that 
very few cases of pernicious anaemia are ever met with, but that 
such cases are, in reality, the symptomatic expression, the appa- 
rent manifestation of some general morbid condition of the 
system, which may be ranged under one of the diatheses with 
which you are acquainted. Cancer exists in some cases ; again, 
and oftener, the patients are tuberculous or consumptive. These 
are the two great constitutional maladies which oftenest induce 
pernicious anaemia. And this is so true that I have been able to 
make the diagnosis without any very market I local signs of a 
tuberculous affection, simply from this progression, this lata! it v, 
in the course of a case of anaemia. I have called it a state of 
anaemia attending consumption. Since then, taking into consid- 
eration this view of the subject, a correct diagnosis has been 
made in a number of cases. 



322 PRINCIPLES AND METHODS OF THERAPEUTICS. 

My young friend, Dr. Lupine, of Lyons, has met with cases 
which seem to confirm this view of the subject. Conse- 
quently, if this view is correct, the great number of cases of 
pernicious anaemia leave traces behind them. It is possible 
that while the patient lives no determination of the cause of the 
disease can be arrived at, but when the autopsy is made tumors 
are met with. Or, as in this case, nothing is found either in 
the intestines or elsewhere. Some cases were cited in which 
death occurred with symptoms of anaemia, and in which abso- 
lutely nothing was discovered at the autopsy, and a case relating 
to an illustrious personage was brought forward. We will not 
speak concerning the real facts of this case ; we will consider it 
simply as related in the account by Alphonse Daudet. In it you 
will find the history of the symptoms observed recounted with as 
much fidelity as he could bring to bear on the subject. 

As we are contemporary, as these facts are of recent occur- 
rence, we know that if no considerable lesions were found, 
perhaps the cause of death might have been excess in the use 
of mercurial preparations. This supposition corresponds with 
rumor, and there was good reason for suspecting it. 

And this was the fact brought forward! When circum- 
stances are so doubtful should such a case be brought forward as 
a scientific fact ? To sum up : you can see that the objections 
made have no great weight, are not of great force, and do not 
stand before a scientific examination of any precision. 

To resume the facts in the case we have been considering: It 
is impossible to establish absolutely and rigorously the demon- 
stration of poisoning. But if we unite this ensemble of facts 
on one side, all the symptoms which accompany the introduction 
of somewhat large doses (say, for instance, five centigrams) of 
arsenious acid per diem, symptoms with which we are well 
acquainted from having observed them in the treatment of inter- 
mittent fever; if we consider the presence of such symptoms, 
their constant repetition under similar circumstances; if we add 
to this, that no organic lesions capable of producing death have 
been found ; if at the same time it be found that the digestive 



ARSENIC. 323 

organs are not putrefied j if, finally, it is said that a sufficiently 
considerable quantity of arsenic has been found to enable a very 
skillful chemist to affirm that four milligrams could be collected, 
surely there is enough to establish a quasi-con viction of guilt. 

I say quasi-conviction, for when the gravity of the affair is 
taken into consideration, it is proper that no possibility of 
doubt exist ; and all the hypotheses imaginable must be passed 
in review before declaring that only one, which is the bad one, 
is proven. In fact, I believe that judgment in this case was well 
rendered and in accordance with the facts, and such was the 
conviction of all who had not allowed themselves to be carried 
away by illusions. 

Now that I have spoken to you at length concerning arsenic, 
I will return to the general question, which has, it might be said, 
been interrupted by the consideration of this case. 

I wished to show you how arsenic penetrates; how it is dis- 
tributed, how it arrives in the interstices of the various tissues. 
After having shown you, by this example, the particulars 
relative to the great and difficult question of the role or action, 
and particularly in relation to the introduction of remedial or 
toxic substances into the system, I will return to the general 
question, by making application of the facts which you have just 
learned. 

What, then, is the course of substances introduced into the 
economy ? I have shown them to you absorbed and in circula- 
tion in the ante-hepatic vessels, delayed in the liver, then overflow- 
ing and carried on in the general circulation, hidden or not by 
the plasma, and, according to the quantity introduced, having 
greater power for the production of toxic phenomena by affecting 
the globules and hindering hrcmatosis; finally, through the 
parietes of the vessels in a free state, or incorporated in the 
plasma, and finishing by becoming incorporated in the paren- 
chyma of the tissues themselves. 

Well, when these substances penetrate into the tissues, they 
may be under various conditions: Sometimes they are simply 
introduced, like water, by interposition ; again, on the contrary, 



324 PRINCIPLES AND METHODS OF THERAPEUTICS. 

they are mixed with the plasma, then they go to take place in the 
tissues, or in the substances called proximate principles, such as 
those which I have mentioned. It is thus that it happens that 
arsenic and other substances follow the same general rules, par- 
ticularly mineral substances. 

But iu such case, what is the mode of distribution ? Why 
does one substance deposit in one place or organ, another in a 
different situation? In virtue, as I have already said, of chem- 
ical affinity, substances substitute themselves one for the other. 
Thus, phosphorus may be substituted for arsenic, as, also, anti- 
mony, which very much resembles arsenic, though it be a metal. 

Chlorine is normally present in the economy, and bromine 
aud iodine may, in part, replace it ; substitution occurs in the 
different compounds, and in the different tissues which contain 
these same compounds. Selenium may be substituted for sulphur, 
and, again, oxygen and sulphur may be substituted one for the 
other. Calcium, another substance normally present in many 
tissues, as you are aware, may be replaced by strontium, by 
barium, and by lead ; and for the same reason that I predicted 
in advance that arsenic would be found in the nervous system, I 
am convinced that barium and lead would be found in situations 
where calcium is present. Iron is normally present in the 
economy. Manganese may, in a certain number of cases, be 
substituted for it, so that if chl orotic patients are not benefited 
by chalybeates, their systems may be improved by introducing 
considerable proportions of manganese. Consequently, here is 
another proof of these chemical and physiological substitutions. 
Zinc might, even, be considered as taking the place of these two 
metals. This is, then, what happens for the metals ; I am con- 
vinced that something analogous happens for organic compounds, 
for those species of radical substances which may be substituted 
one for the other in the chemistry of the living organism. 

I will now speak to you of certain facts which do not find any 
parallel in the history of arsenic. You have seen arsenic taking 
its place in the tissues, but you have not seen it produce effects 
analogous to those induced by certain substances which act 



ARSENIC. 325 

simply as bodies infiltrating the histologic elements, or as bodies 
which are simply dissolved in certain other substances normally 
present. Thus, for instance, alcohol, ether and chloroform 
possess, as you know, the property of dissolving fatty bodies. 
When poisoning by these substances has taken place, they are 
found in large proportion in the brain, exactly as if they had 
come in contact with a substance with which they have a species 
of affinity. This fact is repeated for the alkaloids. The singular 
analogy existing between the alkaloids, proteic substances and 
fatty matters has been demonstrated. 

It seems as if the alkaloids were intermediary between fatty 
and proteic substances. They also deposit themselves in the his- 
tologic elements of the nervous system, and it is on this account 
that they induce so marked effects during the period they are 
there present. 

These three modes: imbibition, a sort of amalgamation and 
penetration of analogous molecules, which act by dissolving one 
another and finally undergoing chemical integration with organic 
tissues; such are the three different modes by which active sub- 
stances penetrate into the economy. But there is another man- 
ner, very interesting, which has long been known, but the inter- 
pretation of which is difficult. I have shown you that substances 
which during a certain period are in the state of principles foreign 
to the economy, may become united with some of the tissues, 
but are mobile, and after a time are evacuated. 

But in other cases where mineral substances have been intro- 
duced a portion is irremediably immobilized ; it remains in one 
place, and while all about it changes, it remains in the same state. 
For instance: when silver is administered— the nitrate of silver 
given to paralytic and ataxic patients, to subjects in tabes 
dorsalis — when the drug has been taken for a sufficient length of 
time, at first a simply grayish coloration is observed, which soon 
becomes darker, and finally the skin may acquire an olive 
tint. It is difficult to understand why, when this coloration is 
produced, it should in the end become dark and indelible. 

Aslhave already said, and I repeat, there is but one phenomenon 



326 PRINCIPLES AND METHODS OF THERAPEUTICS. 

which will occur with certainty when silver is administered 
under these conditions; that is, this disagreeable coloration of the 
skin. When the matter inducing this tinge is examined, it is 
seen that it is composed of silver under a form not easily deter- 
mined; to some observers it is an albuminate; to others, a chloride; 
others, again, consider it silver reduced to the state of an oxide. 

But the fact is, once deposited in or thus mixed with the deeper 
elements of the superficial layer of the skin, the metallic substance 
remains fixed. And this, which is true for silver at the periphery, 
happens also for internal surfaces. It causes staining of the gums, 
just as does lead. When caused by lead a different coloration is 
observed in the gastro-intestinal mucous membrane. These deposits 
are very strange, for how does it happen that while the pigment 
cells themselves disappear, these spots produced by mineral sub- 
stances do not disappear? It is difficult to determine why, but 
the fact is certain. You see, then, that certain metallic deposits 
are produced after the internal administration of substances which 
are capable of forming compounds or insoluble substances. 

I wish in the next place to speak of the manner of elimination 
of the various substances thus introduced into the organs. There 
are substances, as I have said, almost in the free state, simply 
dissolved in the plasma; and others which form an in- 
tegral part of certain organs. Those which are free are taken 
up with great facility by the circulation, and appear very soon 
in the excretions; those, on the contrary, which are attached to 
any organ, can enter but tardily into the circulation. It is thus 
with substances which may become substituted for principles nor- 
mally present; you will see such substances long delayed. I have 
given you the limits for arsenic. You will find that they are 
longer for other substances. This elimination is accomplished in 
two ways : Sometimes they are introduced into organs which I 
call caducous — the nails, the hair, the epithelial surfaces — and they 
are thrown off with them. 

It is the same phenomenon seen in plants; th leaves serve 
them as means of elimination for mineral substancer Thus the 
mineral substances entering a tree are in great quantity; 



METALLIC DRUGS. 327 

nevertheless they are not found afterwards in the wood, because 
they are deposited in the leaves, which, like hair, are caducous 
(or destined to fall). When, on the contrary, the substances are 
fixed in elements belonging to permanent organs, then they re- 
main just as long as the histological elements, of which they form 
a part, themselves last. 

Unfortunately, we are unacquainted with the length of time 
that histological elements last. We know that the blood globules last 
but a few days, but it is probable that other histologic elements 
last longer ; consequently we cannot determine, in advance, how 
long mineral substances accidentally forming part of them may 
sojourn in the system. I have said that there are substances 
which remain longer than arsenic. It is necessary to say, gen- 
erally, that these are mineral substances, precisely because they 
take a permanent place in the tissues, and particularly, because 
they act as alteratives, agents which I designate as metatrophic. 

Let us consider, as examples of substances of rapid elimination, 
the alkaloids. These are organic matters which take no part in 
the formation of tissues, and which are speedily eliminated in a 
few hours, or, at the latest, in a few days. The different salts, 
bromides, iodides, or the neutral salts, are eliminated also with 
great rapidity. But the mineral substances are, I repeat, long 
delayed. Thus iron, which enters the globules, manganese, 
mercury, antimony, arsenic, copper. 

I have said that arsenic might not disappear for thirty, 
thirty-five, or even forty-five days; Orfila said fifteen days; but 
I have shown you that after forty-five days there was still arsenic 
present. Antimony remains three months in the economy; 
copper and mercury six, seven, or eight months. 

During the period of their sojourn these substances produce 
their alterative effects. Consequently, such medicaments can be 
considered as producing effects for a long period of time. 

It is difficult to demonstrate what becomes of sulphur, or 
phosphorus, when excessive doses are employed ; but it is possible 
that they enter and become an integral part of various organs, 
act like metals, and sojourn there for a long period. 



328 



PRINCIPLES AND METHODS OF THERAPEUTICS. 



It has been remarked by physicians, at mineral springs, that 
the effects of these waters have a duration of several months, 
and it is not necessary to recommence the treatment until such a 
period has elapsed, as is required either for sulphurous waters 
or for phosphorus, when a purely medical treatment by them is 
undertaken. 



ELIMINATION OF MEDICAMENTS. 329 



CHAPTER XXVI. 
Elimination of Medicaments. 

Variable sojourn of different substances in the organism ; causes of this vari- 
ability ; variable rapidity of elimination. 
Choice of elimination made by medicaments. 



It is not easy to understand why different substances remain 
so long in the economy. There are, however, certain circum- 
stances which might be mentioned to explain this sojourn. 

In the first place it is evident that the more thoroughly the 
substances penetrate into the organism, the longer will be their 
sojourn. If it is a volatile substance, acting on the globules, it is 
clear that the incessant exchange of gases going on in the interior of 
the organism will cause the speedy separation of these substances 
and their consequent disappearance from the economy. This is 
what generally happens, even for the oxide of carbon, unless it kills 
the subject. When it is present in feeble proportion, after a certain 
number of hours, in an atmosphere properly renewed, t he symptoms 
due to its presence will be dissipated. If, on the contrary, substances 
enter the interstices of the different organs, without taking part 
in tissue formation, they are even then very subject to be taken 
up by absorption and to disappear with considerable rapidity. 
Those which remain longer are such substances as penetrate 
into the histological elements themselves, that is to say, into the 
fundamental substance of these elements. 

What causes the length of the sojourn in the last case? Is it 
due to the longevity of the histologic elements? It is difficult to 
express a fixed opinion on this subject. We know that certain 
elements do not long resist. In the foetus the globules may be 



330 PRINCIPLES AND METHODS OF THERAPEUTICS. 

in considerable proportion, and disappear with great rapidity. 
In 48 hours the proportion may fall from 900,000 globules to 
600,000. I know well that these are conditions differing from 
the normal state; but it is well known that the globules are not 
long lived. But evidently solid histologic elements should last 
much longer, and it is highly probable that this is one of the 
reasons why remedial or toxic substances make so long a sojourn 
in the economy. 

It is probable, also, that the degree of solubility or insolubility 
of a substance has a marked influence on the prolongation of its 
sojourn. We have just seen that metallic substances may have a 
very long sojourn. Thus individuals submitted to the nitrate of 
silver treatment never become completely white, and live often 
many years having the same coloration of the skin. 

You may also take a substance intermediate between this state 
of absolute insolubility and a state of very great solubility j if 
you have a substance of semi-solubility, it is evident that it will 
be difficult to return such substance into the circulation. 

It is probably thus that iodide of potassium acts ; this drug 
having been recommended by Natalis Guillot and Melsens, to 
bring back into the circulation an enormous proportion of arsenic, 
when for several days this substance has no longer appeared in 
the excretions. Perhaps it promotes the solubility of the ar- 
senical substance, which can be thus eliminated. Nevertheless, 
there is another manner of interpreting these phenomena; iodide 
of potassium possesses the remarkable property of promoting 
denutrition, of thus diminishing swellings, hindering production 
of hypertrophies, reducing hyperplasia. It is thus that iodide 
of potassium renders such great service in all hyperplastic affec- 
tions, and in that affection particularly remarked for inducing 
hyperplasia, syphilis in its third period. 

I have maintained that iodide of potassium, causing disintegra- 
tion of remedial agents, should be considered as rendering denu- 
trition more active, favoring the general round of nutrition, 
aiding in the disposition of the matters thrown off during the 
nutritive activity of the histologic elements ; that is to say, those 



ELIMINATION OF MEDICAMENTS. 3-31 

substances having undergone regressive changes, and at whose 
expense urea and uric acid are formed, and at the same time 
aiding also to dispose of the mineral substances which have 
made a part of these elements for a period. 

There is, then, a chemical and physiological manner of inter- 
preting this action of iodide of potassium ; but I place both one 
and the other before you with great reserve, as there is no true 
experimental basis for either view. 

That which N. Guillot and Melsens saw has likewise been 
observed by everybody ; the drug causes the medicaments to re- 
enter the circulation; but there are two possible explanations of 
the fact j the one which they have given and that which I pro- 
pose to you. 

There is another point of view under which we should con- 
sider the subject. We have just spoken of the duration of the 
sojourn in the tissues ; it remains now to consider why certain of these 
substances appear so speedily in the excretions and others arc so long 
delayed. How does it happen that one substance in the bladder or 
stomach undergoes absorption and appears, sometimes after three 
minutes, in the saliva or in the urine, while another, under the 
same conditions, will not appear for a day or for forty-eight 
hours ? 

This rapidity or slowness of appearance of substances used 
as medicaments is due to various causes. In the first place, 
the organ or tissue in which the substance is located is 
not without its influence. It is clear that a substance which 
has an affinity solely for the histologic elements, and penetrates 
into these elements, can appear in the secretions only after a 
lapse of time. But when substances are arrested almost on 
entering, when they are simply carried on in the circulation and 
penetrate the meshes of cellular tissue, or the cellular inters! 
of the tissues, then it is less difficult to understand how certain 
substances appear so speedily, and others so slowly in comparison. 

There are two principal causes which govern this rapidity or 
tardiness of appearance in the secretions; the first of these causes 
is the tolerance of the system for the substance; the second is the 



332 PRINCIPLES AND METHODS OF THERAPEUTICS. 

quantity of the substance present at one time in the economy. 
The tolerance is in relation to the nature of the substance, and 
we will explain what is meant. It is not through its mineral or 
vegetable nature that a substance acts ; it is whether it may be 
of a homogeneous or heterogeneous nature as regards the organ- 
ism. Thus Fourcroy has the priority in saying (I think he was the 
first to make the observation, though it is so long ago that I 
speak from memory only), that the soda salts should be accepted 
with more facility by the organism, as they exist in all the tissues 
in great abundance. 

I have myself written (I ask permission to cite myself; it is 
long enough ago to have become historical) : " It may be held as 
a general rule, that medicaments are ejected with so much the 
more rapidity, the more they differ from the principles which 
normally constitute the organism. Thus the potash salts, more 
heterogeneous in the blood than those of soda, are tolerated with 
greater difficulty in this liquid, and are sooner ejected from 
the economy."* These assertions, or this law, is exceedingly clear. 

That which I wrote at this period has been amply verified, 
and experiments on animals, as well as observations in the human 
subject, have demonstrated the truth of the assertion. 

Thus, our great physiologist, Claude Bernard, has shown that 
the soda salts are much better tolerated than those of potash. 

Further experiments, repeated by a number of physiologists 
and chemists, have shown that this is a general fact concerning 
the soda salts in all the animals on which experiments are made 
in the laboratory. 

This same fact concerning the toxic effects of the potash salts 
has been shown by different chemists, and Guldman has even 
demonstrated that the salts of potash render slower and enfeeble 
the cardiac contractions. It is on this account that they have 
been considered to have a toxic effect on the muscles. But this 
only expresses the fact, without explaining it. Why should 
this be so ? It is because there is potash in the muscles, and for 

* Gubler, " Commentaires Therapeutiques du Codex." 2d edition, Paris, 
1874. 



ELIMINATION OF MEDICAMENTS. 333 

this reason these salts are attracted toward them. And, finally, 
there is such a quantity present that there results a marked 
excess, which acts in opposition to the regular progress of nutri- 
tion and denutrition in the muscles. 

The same facts may be observed for other substances: thus, 
the chlorides are better tolerated than the bromides, and these, 
again, better than the iodides. It is always for the same reason ; 
there is abundance of chloride of sodium in the organism ; on 
the contrary, no bromine, or very little, is present ; it is the same 
for iodine. I do not say that it is impossible to find these ele- 
mentary bodies in the organism; and certainly more would be 
found if vegetables containing these principles were made use 
of, for the minerals found in the organism but show the manuer 
in which it is nourished. 

I am convinced that in an inhabited planet containing manga- 
nese, more of the metal w T ould be found in the organisms of the 
inhabitants than iron. In our planet iron is the predominant 
metal, and the salts of iron are better tolerated than those of 
copper. Again, there exists a very curious fact, interesting for 
the physiologist and the therapeutist, which is that the glucose 
found in the urine is much better tolerated than grape sugar. 
Very instructive experiments have been made on this subject, 
which lead the way to more profound study regarding the 
action of medicaments and poisons, and illustrating, also, the 
manner of undertaking this study from a chemical point of view. 

Thus these two forms of sugar — grape sugar and diabetic 
sugar — are identical from a chemical standpoint. They are cons! i- 
tuted of carbon and hydrogen in the same proportion-, 
when Claude Bernard injected diabetic sugar into a large dog, and 
observed what happened in the urinary secretion, he did not 
find any sugar appear in the urine; on the contrary, when li<> 
injected twenty grams of grape sugar into the same dog, he re- 
marked that the dog instantly became, for the moment, diab 
sugar being found in the urine. 

This experiment has been repeated in various ways and has 
always given the same results. 



334 PRINCIPLES AND METHODS OF THERAPEUTICS. 

It is evident that diabetic sugar is, as might be said, toler- 
ated as a normal element, while grape sugar acts as a foreign 
body. 

You can thus see that the tolerance or intolerance of the econ- 
omy for a substance may be explained by considering whether 
the substance is homogeneous or heterogeneous as regards the or- 
ganism which receives it. 

How is this more or less rapid elimination explained, if we 
put aside influences above mentioned which control the duration 
of its sojourn? Here are the elementary phenomena, to which 
may be reduced the modifications offered by various substances : 
Three orders of facts £re observed. There is, as you have just 
seen, absence in the secretions of the substance introduced into 
the organism, or, on the contrary, it appears in the secretions 
These are two absolutely contrary phenomena, remarked often 
when the tolerance for the substance is extreme or the intoler- 
ance very marked. Or there may be more or less rapid appear- 
ance of the substance. Thus, sometimes the substance is wanting, 
or is in the latent state in the economy ; nothing in the secretions, 
no modification is revealed; or, on the contrary, it appears in them 
more or less speedily. And, appearing thus with more or less 
rapidity, it causes more or less irritation in the organs of secretion. 

Again, another phenomenon is observed under these conditions; 
more or less excitation of a secretory organ, causing hyperemia 
through hypersecretion. In other words, the substances intro- 
duced into the economy and eliminated therefrom may determine 
either (1) a very exaggerated secretion, or, (2) they may produce 
hardly any effect on the organ, or (3) the elimination occurs 
in a more or less lengthened period of time. I am about to give 
you examples of these various cases. 

As examples of the non-appearance or the rapid appearance, I 
have already instanced diabetic and grape sugar, substances 
which appear to be similar, but which, in reality, diifer widely 
as regards the living organism ; that is to say, that notwithstand- 
ing their being of the same composition, they have different 
dynamic properties. 



ELIMINATION OF MEDICAMENTS. 335 

As examples of the greater or less rapidity with which substances 
appear in the secretions, there are some, as iodide of potassium, 
which appear after three or four minutes. Thus, in experiments 
made on the bladder, not in the normal condition, for then it does 
not absorb, but when in a morbid state, with ulcerations, conse- 
quently in excellent condition for absorption; in such experiments 
by Segalas, and Demarquay, it was found that iodide of potassium 
injected into the bladder appears, after three minutes, in the saliva. 
Consequently, if you take into account that a minute is neces- 
sary for the substance to make the round of the circulation, you 
may see that absorption took place with extreme rapidity. Four 
or five minutes is a delay which is rarely met with, even when 
the substance is introduced into the stomach. Bromide of potas- 
sium is eliminated less speedily, in ten, twelve, or fifteen minutes. 
And, take notice, that these are two salts which resemble each 
other very much; but they differ not by any dialysable property 
not in their constitution; it is always potassium and a metalloid ; 
but one is more heterogeneous than the other. Chlorate of potash 
is eliminated more slowly than bromide of potassium, but not 
always; sometimes the latter takes more time. 

Again, the corresponding soda salts are slower of elimination 
in a notable degree. Thus, if you take iodide of sodium, or bro- 
mide of sodium, they are delayed twice as long in the system as 
iodide of potassium. It is the same for carbonate of sodium, as 
compared with carbonate of potassium. 

Practical conclusions can immediately be drawn from these 
facts. If you wish to exercise a topical action on the emunc- 
tories, to which salt will you give preference, to soda salts, or 
to those of potash? To a substance resembling thos<> present in 
the economy, or those differing from them? You will evidently 
make use of a heterogeneous substance, and consequently of pot- 
ash salts, if your choice lies between the salts cf potash and those 

of soda. 

Again, observe what happens with diuretics, as the nitrate 
of potash, silicate of potash, the bromide of potash, even, a diu- 
retic that I have utilized in the Beaujon hospital, and which is 



336 PRINCIPLES AND METHODS OF THERAPEUTICS. 

appropriate for a certain class of subjects in whom the kidneys 
are irritable. These potash salts are more diuretic than the 
corresponding salts of soda. 

The nitrate of soda and acetate of soda have been employed ; 
these would be low-priced diuretics, but have not the value of 
nitrate of potash. 

To compare the bicarbonate of potash with the bicarbonate of 
soda ; the first is powerfully diuretic. If you take even mineral 
waters which contain a considerable proportion of carbonate of 
soda, with little potash, they will be more diuretic than others 
which contain much more of the two salts, but chiefly of 
bicarbonate of soda. If, for instance, you take the waters of 
Vals, containing five or six grams of bicarbonate of soda, you 
will find them less diuretic than the waters of Vichy, which 
contain five or six grams of bicarbonate of soda, and fifty centi- 
grams of bicarbonate of potash. 

If you wish speedily to render the urine alkaline it is to a 
potash salt that you will give preference, because it is that which 
causes the urine to pass more rapidly, excites more the renal 
secretion, causes a greater proportion of the salt to be found at 
one time in the organ which eliminates it, and, consequently, in 
the urine. Something similar may be said of the chlorate of 
potash as compared with the chlorate of soda ; it is unfortunate 
that the former has so little solubility. Chlorate of soda presents 
a considerable degree of solubility as compared with the potash 
salt, but it does not produce the same effect on mercurial stoma- 
titis, and particularly on ulcero-membranous stomatitis, which is 
so speedily modified by chlorate of potash. It does not produce 
the same effect, because it is very slowly eliminated ; to produce 
a considerable modifying action, like chlorate of potash, it would 
be necessary to introduce it in very large doses. If, on the 
contrary, you wish to exercise a profound modifying action on 
the economy, if you wish to produce alterative effects, which I 
have styled metatrophic, an opposite course must be pursued ; 
heterogeneous substances must not be used, for they, it might be 
said, incite the organism to rebellion : from their nature they 



ELIMINATION OF MEDICAMENTS. 337 

necessarily undergo rapid elimination. Preference must, then, 
be given to soda salts above potash salts always, when it is 
possible. It is preferable at all times to introduce into the system 
compounds which differ the least from the elements of the living 
tissues. 

You will have to establish the inverse rule as regards the 
iodides, the chlorides and the bromides, and give the prefer- 
ence to the chlorides for the introduction of a metallic substance, 
rather than to the iodides. If you wish to increase the rapidity 
of the denutrition, to render secretion more active, to induce 
greater activity in the excretions, then the iodides should be 
brought into play. Of how long duration is the process of 
elimination of these various substances, some homogeneous, others 
heterogeneous? Just as heterogeneous substances appear most 
speedily, so they are most speedily eliminated. These are two 
facts which go together ; for instance, if we take iodide of potas- 
sium, which is more heterogeneous than the bromide, in a few 
hours all is eliminated ; and in a greater number of hours the 
bromide, also, will be almost completely eliminated, so that it 
will be difficult to demonstrate its presence. When chlorate 
of potash is used, it is partially transformed into chloride 
of potassium, and not less than thirty-six or forty-eight hours 
are necessary for the elimination. 

But there is one singular fact in the history of medicaments ; it is 
the almost constant direction that each one follows. Why does a 
medicament follow almost invariably the same route of elimina- 
tion? one the respiratory organs, another the biliary apparatus? 
For a lono- period it was considered sufficient to simply observe 
the fact in an empirical way. I have thought that it might be 
possible to introduce a physiological reason which casta consid- 
erable light on all these phenomena which are of very difficult 
interpretation, and I have remarked : elements introduced into 
the system from without follow the route where similar elements 
exist in the economy, or of analogous substances, if any analo- 
gous elements are present, lam about to sh>\v you that this 
view is verified in all the several cases, and that it oermitd us to 

22 



338 PRINCIPLES AND METHODS OF THERAPEUTICS. 

foresee by what avenue any remedial substance which you have 
introduced will escape. 

We will, if you wish, pass in review the principal secretions. 
The saliva and the pancreatic secretion contain the neutral 
salts, a little chloride of sodium and a small quantity of soda. 
The bile contains soda, it contains various fatty matters and the fat 
taken with the food, for margaric and oleic acids have been 
found in it, without considering the various substances peculiar 
to the bile, choleic and cholic acids, and many others. In the bile 
there is found also resinoid matters, a pigmental substance pos- 
sessing varied properties, so that it has been divided into a cer- 
tain number of chemical principles. Hsematoidin is often found 
in considerable quantity in old cysts of the liver. The sweat 
contains much water, carbonic acid, volatile fatty acids, and acetic 
acid ; with these it contains neutral salts, a small quantity of 
urea, and of uric acid, in individuals whose systems are over- 
charged with these products. 

The urine contains much water, neutral salts, and acid in a 
free state, a small quantity of fatty matter, of which I have de- 
monstrated the presence ; and also, in a certain number of cases 
a ferruginous pigment. 

Milk contains sugar, fatty bodies, mineral principles, neutral 
salts in great quantity, and an albuminoid substance. 

We will reconsider the various secretions, and take up one 
by one the consideration of the substances that we find neces- 
sary to introduce into the economy. We often introduce alka- 
loids, we introduce salifiable substances, or neutral salts. By 
what route will these substances be eliminated? By almost 
every emunctory, since you see that almost all the secretions 
contain neutral salts; consequently, the salified alkaloids pass 
by all the organs of excretion. Nevertheless, there are routes 
more particularly followed by the various series of alkaloids. 
Those which are fixed pass rather by the kidneys, those which 
are volatile by the respiratory organs. Thus conine and the 
alkaloids of the umbelliferse pass by the organs of respiration. 

If you wish to have the action of the substance at the moment 



ELIMINATION OF MEDICAMENTS. 339 

it leaves the system, it is better to introduce into the circulation 
volatile substances which take the respiratory organs as a route of 
excretion. 

Although the neutral salts are eliminated from all parts, there 
are, however, certain routes of issue always wide open ; for in- 
stance, the urine and the neutral salts pass almost entirely in this 
fluid. And I would assimilate with these neutral salts other 
substances, as the resins, and the cantharidate of soda, which 
is transformed into cantharidin, and passes with the neutral salts 
in the renal secretion, thus producing the disorders with which 
you are acquainted. Let us take, as examples, the metals and 
the metalloids. By what route will they pass ? I have shown 
you which organs or tissues in the normal state contain iron, and 
iron is the only metal normally present. 

It is probable, however, that if manganese or copper were ad- 
ministered by kilograms, these metals might be found in the 
blood, but nothing is known concerning such a case. 

The metals, then, follow in elimination the route by the bile 
and the urine; by the bile in particular, because in the bile there 
is still more ferruginous pigment than in the urine. 

You can see how generally this rule can be applied, how it 
assists the memory at the same time that it strikes the mind. 

We will make an application of the rule to arsenic. It es- 
capes particularly in the bile, so much so, that when there is but 
little in any other organ, it is there that it should be sought ; 
and not only in the hepatic parenchyma, but also in the flow of 
bile. 

This fact has been demonstrated in the experiments made 
at the physiological laboratory of the Faculty by MM. Lab 
and Bonnefoy. I repeat, that when small quantities of arsenic 
are introduced into an animal, it should not be sought elsewhere 
than in the bile. You see that it is very important to be ac- 
quainted with this rule, which suffers certain exceptions, but 
these exceptions themselves have their origin in other rules, as I 
will attempt to demonstrate to you. 

Fatty matters are excreted in the bile, the milk, by the seba- 



340 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ceous glands, and in small quantity in the urine'. Resins are 
eliminated in the bile, where considerable quantities are found. 
And remark this : a large number of resins are cholagogue. A 
great number are drastic purgatives, because they act on the 
mucous membrane of the digestive tube and provoke symptoms 
of hypercrinesis ; but when not very considerable doses are em- 
ployed, which do not produce their effects until long after their 
introduction into the primse vise, they owe their late action to 
having been secreted by the liver, eliminated by the bile, and 
arriving then in the intestines, produce their usual effects. 

By what organs are the acids eliminated? We have seen that 
two liquid secretions are acid : the sweat, the principal one as 
regards the acids, and then the urine. Thus, it is a method 
among the vulgar in the North, and in many places (the manner 
alone differs), to plunge a red-hot iron into a mug of beer ; the 
iron induces ebullition, which leaves the beer slightly soured (I 
have tasted it ; I found it disagreeable, but it is considered deli- 
cious), and thus drank, while heated, it induces abundant perspi- 
ration. Where wine is common in a country, wine thus rendered 
sour is used. 

Is it not curious that, by considering the rules of applied 
physiology, we, in the end, understand the vulgar methods of 
treatment which physicians ridicule when they do not understand? 
Thus you will no longer laugh at this practice when you are 
aware that acetic acid is eliminated by the sudoriparous glands, 
excites the secretion of these same glands, and determines irrita- 
tation and redness. The acids are also eliminated by the renal 
glands, so that by introducing into the economy phosphoric acid 
the acidity of the urine may be augmented, and urines of neutral 
reaction rendered acid. 



ELIMINATION OF MEDICAMENTS. . , | | 



CHAPTER XXVII. 
Elimination of Medicaments {Continued). 

Influence of different doses ; practical applications. 

Under what form substances are eliminated, intact or more or less trans- 
formed. 



Gentlemen: 

It is necessary for me now to speak concerning the influence 
of the quantity taken on the rapidity of elimination. 

When heterogeneous substances are considered, that is those 
which are not analogous to the principles present in the economy, 
a very small dose may possibly be tolerated; it passes, as might 
be said, unperceived. Suppose ten centigrams of iodide of 
potassium be taken; there will be no increase in the renal secre- 
tion and no appearance of iodide in this liquid; but just in pro- 
portion as the quantity of the substance augments, the rebellion 
of the various organs increases, for they take up the medicament 
only to reject it with great energy. And in such cases you will 
have almost instantaneous appearance of the active substance in 
the products of secretion. It is thus, when you introduce a gram 
of iodide of potash, that very promptly, say after three or four 
minutes, it is found in the urine. 

Consequently, you can see that the dose has considerable influ- 
ence as regards the tolerance of the economy for a medicament. 
And this explains why, when a considerable dose of a substance 
is introduced at one time into the system, during the first 
of its action, say during a few hours, considerable quantities of 
this substance are eliminated, while, on thecontraiy, what remains 
will require a much longer period for elimination. Yon will 
have seen half the iodide eliminated in the first three or four hours ; 
the second half will require the following twenty-four hours. 



342 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Take sulphate of quinine ; many physicians give fifty centigrams 
at one time. "When these large doses have been introduced, the 
medicament appears in the urine after twenty minutes, and much 
passes during the first four or five hours; then elimination be- 
comes slower, and finally, the third day, a certain quantity of the 
alkaloid is yet met with in the urine, but is found to be in very 
small proportion, and the elimination is prolonged in a manner 
which would not have been expected if we were not acquainted 
with the law that elimination is more rapid in proportion as 
the quantity of the substance saturating the economy is more 
considerable. 

The homogeneous substances, on the other hand, can be toler- 
ated in pretty large quantity; it is only when the dose is enormous 
that they commence to be eliminated. Much chloride of sodium 
can be injected before it manifests its presence by an excess of 
chloride in the urine, but a moment arrives when its excess in 
the system will be shown by the passage of a larger quantity in 
the urine. It is the same for sugar. You know what happens 
for individuals predisposed to diabetes : if they eat a moderate 
quantity of sugar, there will be no notable effect produced on the 
urinary secretion ; if they eat substances containing considerable 
proportions of sugar, the contrary will be the case. 

The same holds true in albuminuria : if the patient eat, as did 
Claude Bernard, twelve hard-boiled eggs, albumen will be found 
in the urine. 

In the same way those who eat candies in large quantities 
may, for the moment, become diabetic. But, I repeat, it is only 
when the dose of a homogeneous substance is enormous that it is 
seen to pass into the secretions with rapidity. 

The practical inference to be drawn from what I have said 
regarding the quantity of active principles ingested as remedial 
agents, can be stated as follows : if you wish to determine 
topical effects on the various emunctories, it will be necessary to 
employ substances very different from those found in the econo- 
my, and to employ them in large doses at a time. 

If you wish, on the contrary, to produce effects through the 



ELIMINATION OF MEDICAMENTS. 343 

diffusion of the drug in the economy, and particularly alterative 
effects, that is, if you wish to modify in a slow, sustained man- 
ner the living economy, it is necessary to employ substances 
resembling as much as possible those normally present, and to 
employ them in small, repeated doses for a considerable period 
of time. It is possible, no doubt, that with heterogeneous sub- 
stances, employed in very small doses, you may find sufficient 
tolerance to produce metatrophic effects ; just as with large doses 
of a homogeneous substance you can determine topical effects on 
the emunctories. But the reunion of these two conditions — a 
heterogeneous substance in very large doses, to produce topical 
effects, a homogeneous substance in very small doses, to produce 
general and alterative effects on the system — these are the condi- 
tions it is necessary, if possible, to realize. And examples de- 
monstrative of the truth of this statement could be brought 
forward. Thus, for instance, mercury, if employed as iodide of 
mercury, will necessarily give rise to many phenomena during its 
excretion ; it causes salivation and symptoms of stomatitis in the 
mouth and gums. On the contrary, chloride of mercury is a 
substance which does not affect the mouth, and which does not 
induce the phenomena during its excretion observed with metallic 
mercury. You see that interesting applications could be made. 
Again, you are all aware that one of the advantages of mineral 
waters is to produce slow but profound effects, modifications an- 
alogous to those produced by alteratives. The mineral waters give 
with most facility all the symptoms induced by trophic changes. 
In the paludal cachexia observed in swampy countries you make 
use of the mineral waters, that is, of solutions which do not 
contain active principles in large proportion, and which, being 
taken for a considerable period determine, in the end, very 
extensive and very profound general phenomena. I rest rut 
myself to these general considerations, which appear to me suffi- 
cient to establish the importance of the distinctions which we 
have indicated. In considering the various routes of elimina- 
tion I passed in review the neutral salts, the metals, fatty 
substances, the resins, the acids, and I demonstrated that, through 



344 PEINCIPLES AND METHODS OF THEKAPEUTTCS. 

physiological indications, the organs selected by them for elimi- 
nation could be determined in advance. 

In order to terminate this enumeration, it only remains for me 
to speak to you concerning gaseous substances and volatile 
principles, that is, gases and substances in the state of vapor. 

What route can you assign, in advance, for the elimination of 
volatile and gaseous substances? The organs by which they are 
eliminated are all indicated ; they are those by which escape 
principles of the same species : the respiratory organs, on the one 
hand, the sweat glands on the other. These glands, acting in 
conj unction with the organs of respiration, give issue, not only to 
volatile substances, such as the fatty acids, but even to sulphu- 
retted hydrogen and to carbonic acid. At the same time these 
glands take from the atmosphere the gases which compose it, 
and in particular oxygen, which afterwards serves to keep up 
respiratory combustion. I do not say that this phenomenon is 
very marked, but it is notable. It is by these two avenues that 
gaseous and volatile substances escape. In this way are elimi- 
nated carbonic acid, sulphuretted hydrogen, phosphoretted 
hydrogen, and also compounds derived from it, most essential 
oils, as also the camphors properly so called, originating from 
the labiatse and compositse, alcohol, and a number of substances 
equally volatile, ether and many anaesthetic compounds and 
volatile alkaloids. These are all substances eliminated particu- 
larly by the respiratory organs and by the skin, or, at least, by a 
part of the cutaneous glands. 

I repeat, experiment demonstrates this; but the general law 
formulated above would have enabled you to predict that 
this double route would be followed by gaseous and volatile 
substanceSo I now make a few applications to therapeutics. 
If you wish to excite urinary secretion, will you have recourse 
to volatile or gaseous substances ? No; but you know by what 
organs urea and all the neutral salts pass, and also the salifiable 
substances, and the acids capable of taking soda, and thus 
forming salts in their passage, and urea itself, and cantharidin. 
These substances pass out by the urinary organs, and conse- 



ELIMINATION OF MEDICAMENTS. 345 

quently these are the substances which will serve to excite the 
secretion of the renal glands. 

To excite biliary secretion you will have recourse to the resins. 
Most of the resins are drastic substances, which pass by the 
liver; once there, they provoke biliary secretion. So, also, do 
the metals and metalloids. I have even recently cited to you 
new experiments which prove clearly this property of the 
metalloids, and of arsenic in particular, which approaches very 
closely the metals, and is hardly distinguishable from antimony. 
These, in effect, are the substances which most energetically 
provoke biliary secretions. 

Salivary secretion will be provoked by the neutral salts; es- 
pecially by chlorate of potash. 

To excite cutaneous secretion you will recommend volatile 
substances. As a rule, when fatty acids are contained in 
the aliments, as in cheese, there will be excitation of the skin. 
This kind of aliment should, then, be proscribed when treating 
irritative cutaneous affections. You may also employ the gas- 
eous substances when proper. You will excite lacteal secretion 
by the feculents, sugar, fatty bodies, by aromatics even ; it is by 
the skin that substances of this order are eliminated, and milk 
itself owes a portion of its qualities to the aroma it presents. 
This is so true, that milk of excellent quality, as regards chemi- 
cal and microscopical composition, is not well tolerated by 
infants in a certain number of cases, and other milk, of less 
beautiful appearance, seeming not so rich, but good as regards 
the form and small size of the globules, will be better tolerated 
if presenting a peculiar aroma. 

You see that these rules become more evident as we advance, 
and more important. 

Let us suppose that you wish to modify a catarrh of the 
organs of restoration, and the state of local irritation which 
exists in a certain number of affections. To what remedies will 
you have recourse? To aromatic substances, but which arc also 
volatile. Thus, you will employ the essences, and among the 
essences those which cannot be brought to the state of resins. 



346 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Here there is something interesting to say ; that is, that the 
non-resinifiable essences are probably oxygenated essences. Thus, 
take the camphors; they do not undergo oxidation, they are 
oxygenated. There are liquid camphors, such as the essential 
oil of cajaput and the essence of eucalyptus. These essences 
which are oxygenated do not undergo any oxidation, or very 
little, and thus pass almost intact by the respiratory organs. 
And if you wish to act on these organs, it is to them that you 
will have recourse The other essential oils are not completely 
burned, but they are in great part consumed, and particularly 
the spirits of turpentine and Canada balsam. These essences 
become resinified with extreme rapidity, as also the balsam of 
copaiva, and thus they are good solely for the urinary passages. 

If you have to deal with troubles of the sensibility of the 
organs of respiration ; if you wish to modify a cough ; to what 
species of narcotics will you have recourse ? You should give 
the preference to the volatile narcotics, which will act first on 
the nervous system, and locally where they are eliminated. 
So the alkaloids furnished by the umbelliferse are preferable to 
the others, because they have a greater faculty of volatilization. 
You can see what benefits are obtained from syrup of bella- 
donna in hooping cough. You see also what good results are 
given by plants of the family of the umbelliferse, such as the 
phellandria aquatious, which has been considered by Sandras as 
a sort of panacea in chest affections ; it modifies the morbid sensi- 
bility in such cases. I shall say as much for conine and coni- 
cine when we have in France pure products, analogous to those 
obtained by Christison. Do you wish to act on a catarrh of 
the urinary passages ? you will have recourse to analogous sub- 
stances, but having different qualities. Thus, you will employ 
precisely all the essential oils which are rapidly resinified, and 
which, passing to the state of oxides, combine with the acids and 
become true salts ; you will administer them in preference, be- 
cause they will pass, in large part, by the urinary passages. 

It is on this account that copaiva enjoys so much celebrity in 
catarrh of the bladder and urethra. It is on this account that 



ELIMINATION OF MEDICAMENTS. 347 

Canada balsam is also a good remedial agent, while hardly any 
effect is produced in these cases by eucalyptus, the essential oil 
of myrtle, or by the other oils which might be considered as 
liquid camphors. If you wish to produce narcotic effects, you 
will have recourse rather to the fixed than to the volatile alka- 
loids, to morphia rather than to atropia, or other alkaloids origi- 
nating from the umbelliferse. 

One word on the changes which remedial substances undergo 
in their passage through the emunctories. The nature of these 
transformations is little known. It is very probable that a part 
of the changes formerly supposed to take place in the blood are 
really produced in the organic tissues, or in the passage through 
the emunctories. But we can but suppose this to occur, the fact 
has not been demonstrated. 

At the moment the substance escapes from the blood to pene- 
trate into the organs of elimination, just then it becomes sepa- 
rated from the albumen. This is a primary modification. It 
happens also that in the secretions, where the foreign substances 
are mixed with other principles normally present, they encounter 
acids which set them free — exactly as phosphoric acid causes uric 
acid to pass into the free state; this is just what happens for a 
certain number of substances eliminated by the renal passaj 
When the substances are constituted of metalloids having no 
great affinity for their bases, these metalloids may be set free ; 
and this happening when patients take iodide or bromide of 
potassium, a physician with a fine sense of smell may detect the 
odor of iodine. 

The same thing happens for unguents containing iodine and 
lard; they become brown, and exhale an odor of iodine. In the 
respiration it is the carbonic acid which causes the liberation of 
the iodine in a way to determine a very evident odor of iodine 
for a person having a very delicate sense of smell. I have 
already said that substances follow a passage determined in ad- 
vance, and that this passage is the same as that followed by 
analogous or similar substances. There are circumstances under 
which this rule suffers very notable exceptions; Bubstan 



348 PRINCIPLES AND METHODS OF THERAPEUTICS. 

usually following a certain direction no longer follow it, and 
others are forced to pass by certain emunctories where they were 
not expected to appear. 

These are very interesting facts, with a certain number of ex- 
amples of which I am acquainted. Very probably these facts 
are more numerous than is generally supposed at present, for 
from time to time I discover a new example. 

I have shown that the bromhydrate of quinine does not induce 
the toxic effects, the quinic intoxication, produced by sulphate of 
quinine, and it is highly probable that it does not act upon the 
auditory nerve. 

On account of this observation, foreign physicians, in England 
and at Vienna, have had the idea to give bromhydric acid in 
solution, concurrently with sulphate of quinine- and they 
have remarked that under the influence of the bromhydric acid 
thus present in the economy, though it had not been combined 
with the quinine, the phenomena of quinic intoxication habitually 
observed do not present themselves ; as if the acid had given its 
veto and prevented the sulphate from producing the phenomena 
of Meniere's disease. This would be a very curious fact if it 
were verified, but I am obliged to question it, because I have 
not yet succeeded in establishing the reality of this phenomenon. 
It has been asserted by certain foreign practitioners, but in general 
we have more confidence in what we ourselves observe ; and on 
this account my opinion on the matter is subject to a certain 
reservation. 

But here are other examples : it is certain that the presence of 
camphor in the circulation prevents cantharidin from producing 
its ordinary effects on the urinary apparatus. That is to say, 
that if camphor is internally administered, there will be less of 
those phenomena of cantharidism affecting the kidney and 
bladder than under different conditions. This is what experience 
has demonstrated. But I do not mean to say that camphor 
applied on a blister is a good practice. It is, if you wish, a 
means of preventing cantharidism, but it is because the camphor 
thus applied opposes the action of the cantharidin, and that the 



ELIMINATION OF MEDICAMENTS. 349 

greater the quantity of camphor the less the effect produced by 
the blister. I desire, then, to dissuade you from the idea of 
k employing camphor as an application to the surface of the 
vesicating plaster. But it is entirely different when the cam- 
phor is introduced by the stomach, or by inhalation ; then it is a 
practice to be commended. It has been a mooted question as to 
how camphor opposes the passage of cantharidin into the 
urine ; probably a sort of combination occurs between camphor 
and the active principle of cantharides ; but camphor does not 
pass by the kidneys. Thus, considerable quantities may be 
introduced and none at all found in the urinary passages. On 
the contrary, camphor is exhaled by the respiratory organs and by 
the sweat glands And, as it does not pass through the kidneys, 
it opposes the passage, by these organs, of other substances with 
which it is associated. But, in this instance again, I am obliged 
to say that it requires further study to determine whether this 
interpretation of the phenomena is correct. 

I present another fact of a different order, which is very 
interesting. You give a subject iron, under no matter what 
form ; you give him a soluble iron salt with the vegetable acids, 
or mineral acids, or perchloride of iron, or tartrate of potash and 
iron. You will find no trace of iron either in the salivary 
glands or in the products of their secretion. On the contrary, 
you find that the first route taken by iodide of potassium is to 
pass by the salivary glands ; it passes also by the urine. But a 
curious fact: when iron is combined with iodine, when iodide of 
iron is given, or when you give a ferruginous solution contain- 
ing iodide of potassium, you will find iron in the saliva; the 
iodide has compelled the iron to pass by this route. 

These facts are very interesting, but are little known; it is to 
the future and to you that researches on this subject belong. I 
have given you a few examples; they arc sufficient to demon- 
strate the reality of the facts. It seems that if they were more 
numerous and better known, if they were better classed, if the 
interpretation I have given is just, one could know in advance 
how to associate substances in order to force them to pass by any 



350 principles and methods of therapeutics, 

direct route, and prevent them from passing by the organs they 
generally traverse. You can see that there would be a practical 
interest in the knowledge of such facts. 

Substances introduced are eliminated in greater or less propor- 
tion, but they are never found completely unchanged in the 
emunctories, or in the products of secretion; ordinarily there is a 
certain proportion wanting. Is this due to the imperfection of 
our means of finding active substances, or is a portion of the 
substance destroyed in the economy ? Both suppositions are well 
founded. It is very difficult to find even mineral substances in 
the products of secretion. 

We know that a small quantity of mercury or a small amount 
of lead may pass in the urine ; nevertheless, a certain number 
of chemists, having analyzed these secretions, in order to deter- 
mine if they contained a more or less notable quantity of metals 
which they knew had been introduced into the system, have not 
been able to demonstrate their existence in the secretion. 

Consequently, it is impossible to study the form under which 
these substances are eliminated. But there is one consideration 
of importance; physiological laws demand that a certain portion 
of the principles introduced be altered, modified, or even more 
or less completely destroyed. There are three principal cate- 
gories of facts bearing on this point. 

When we have to deal with very stable compounds, particu- 
larly with mineral substances, sometimes even with organic 
principles, or when the affinities are very feeble, the substance 
may pass absolutely unaltered. It is found just as it is intro- 
duced. 

Another case : when the combinations are very unstable, when 
we have to deal with organic, rather than mineral substances, if 
the affinities are very powerful, it will happen, on the contrary, 
that the greater portion of this substance may be altered, 
modified in various ways, and more or less completely destroyed. 

Finally, there are intermediary cases, where, with a certain 
degree of affinity, the substance may be in part altered and in 
part unaltered. 



ELIMINATION OF MEDICAMENTS. 351 

I will pass in review the various categories of substances 
belonging to these three groups. 

To commence with, I will speak to you of substances which 
pass unaltered, or almost intact. These are the carbonates, the 
nitrates, the sulphates, the silicates of potassa and soda ; that is, 
the alkaline salts. These salts pass absolutely without alteration. 
The sulphate of protoxide of iron passes completely unaltered, 
contrarily to what might be believed, while the sulphate of the 
peroxide of iron is reduced. The yellow ferrocyanide of potas- 
sium passes unaltered, while the red cyanide passes to the state 
of yellow cyanide. The sulpho-cyanide passes without altera- 
tion, as do also alum, the chlorides, the bromides, and the 
iodides. 

There are even organic substances which pass without altera- 
tion j thus, the principles which give their distinctive colors to 
indigo, to rhubarb, to gamboge, to the resins of the coniferse, of 
the terebinthenacese, and of the leguminous plants, as the resin 
of copaiva ; sulphuric, nitric, chlorhydric, and phosphoric acids, 
also pass unaltered. 

There are also certain organic principles which enjoy the 
singular property of passing through the economy without 
alteration, being found almost intact in the secretions. 

No scientific experiments have been made to prove this, but 
you will see that the stories recounted by travelers and physicians 
are sufficient to establish it. There are substances so slightly 
altered that the products of the secretion of individuals who have 
taken them are capable of inducing the effects produced by al- 
kaloids themselves. Thus you are, no doubt, familiar with the 
species of false mushroom, which is covered on its surface with 
white spots. This species of false mushroom contains an alka- 
loid which is a poison of great energy. I have, nevertheless, 
eaten it, in order to know what effects would be produced ; and 
I am obliged to say that in certain cases I have remarked dis- 
agreeable gastro-intestinal effects ensue. But it is, at the nme 
time, a substance capable of inducing intoxication, producing a 
drunken state comparable to that induced by alcohol or tobacco. 



352 PRINCIPLES AND METHODS OF THERAPEUTICS. 

In barren countries, as in the most westerly parts of the Old 
"World — that is, in Siberia, and as far as the vicinity of Kouriles 
— there are vast extents of territory where substances capable of 
inducing intoxication are wanting, and where this species of 
false mushroom is considered as something delicious. In these 
countries this false mushroom is employed to produce intoxica- 
tion. All the tribes inhabiting that territory eat this mush- 
room, and prepare a liquor in which this substance enters 
largely. But a strange story which has been recounted by ob- 
servers worthy of belief, is that when an individual has ren- 
dered himself drunk with the false mushroom, and passes urine 
impregnated with it, there is never wanting an amateur near 
him who collects the liquid as it passes, while yet warm, and 
renders himself drunk with it. It would even appear that 
four or five persons have passed, one after the other, partaking of 
the pleasure without having undergone the trouble, that is, 
getting drunk without being obliged to manufacture this famous 
intoxicating liquor. 

These facts, observed by travelers, are very interesting as pre- 
senting such evidence of the unshaken fixity of certain substances, 
even of organic nature, which not only pass through the economy 
without having left anything of their substance, since what has 
intoxicated the one can, after its passage, render another drunk, 
but also without having undergone any alteration. There are 
other substances which, in passing through the system, undergo 
partial modification, but of which a part also passes without al- 
teration. Then again, there is a third category of substances 
which are, in great part, decomposed and destroyed. But it is 
necessary to make a distinction, as regards the modifications 
undergone by substances, into two groups : sometimes substances 
undergo only isomeric modifications, as I have said to you when 
speaking of quinine, which passes in the state of quinidin or 
quinicin ; sometimes there are the different modifications which 
I have described, these combinations with new principles, these 
copulations, when acids are formed at the expense of an essential 
oil, as, for instance, of glucol. Again, there is splitting up of 



ELIMINATION OF MEDICAMENTS. 353 

substances, and true reductions, which are the same as the division 
or splitting up of substances through oxygen. 

Quinine, for instance ; for how long a period was it believed 
that it underwent no alteration and could be found intact in the 
secretions ? 

I leave these facts aside, to take up the oxidations. These 
oxidations carry the substance from the most inferior state 
of oxidation to the most advanced state — that is, until an organic 
principle is transformed into water and carbonic acid. And I 
would say the same thing when considering hydrogen. This 
body causes one organic substance to become sulphurous acid 
and water. These last alterations interest us at present, for they 
lead to the destruction of the substance. 

I have said that there are substances which undergo partial, 
and others complete alteration. For instance, substances which 
are in part burned and in part remain intact ; these are the essen- 
tial oils, which are hydrogenated carbons. Those which are consti- 
tuted at the same time by carbides of hydrogen and oxygen belong 
rather to the preceding category. They resist so much that they 
can be found almost in totality in the secretions. The sulphur- 
etted essential oils are altered with facility ; the sulphur becomes 
oxidized, as do also the essential oils, and they pass, in great part, 
altered and destroyed. The essential oil furnished by asparagus 
is an essence which is partly burned, and in part resists. The 
same may be said of oil of sweet almonds. Tannin, also, is 
in this category; it is a glucoside, producing at first gallic 
acid ; here it becomes pyrogallic acid. Javel water is partly 
oxidized. And in this class alcohol might be cited. You know 
that there have been great differences of opinion as to the 
changes alcohol undergoes. At first, long ago, it was admitted 
that it underwent combustion and became finally water and car- 
bonic acid. But Maurice Perrin, Lallemand,and others assert that 
alcohol traverses the economy without alteration ; that it is found 
in the secretions, and that, consequently, the belief formerly held 
was pure illusion. Two classes of substances may be distin- 
guished, and alcohol belongs to an intermediary series. The 



354 



PRINCIPLES AND METHODS OF THERAPEUTICS. 



conditions under which it undergoes alteration, or, on the con- 
trary, remains unchanged, are easily understood. If very little 
alcohol is introduced, it will not pass unaltered. You will never 
observe the breath of an individual who has drank very little 
wine give the perfume of acetone or aldehyde. Consequently, 
small quantities of alcohol introduced into the system in a 
normal state are burned and disappear, while, on the contrary, 
if you introduce considerable proportions it passes, in great part, 
unaltered. It is under such conditions that a lamp might be 
made to burn with the alcohol of the breath. But these are 
conditions not observed during the hygienic or therapeutic 
administration of alcohol. 






ELIMINATION OF MEDICAMENTS. 355 



CHAPTER XXVIII. 
Elimination of Medicaments, 



Oxidations in the economy. 

Variations in the action of remedial agents. 

R61e of medicaments ; r61e of the organism. 



Gentlemen : 

I will speak to you to-day of substances which are, in large 
part, burned, and which consequently are destroyed in the sense 
we give to the change, for we know that nothing is lost or noth- 
ing created, except as to its form. 

There are certain substances which pass from the emunctories 
completely consumed, they are found in no appreciable portion, 
though it cannot be said absolutely that they are not at all 
present; as they may be found unaltered in exceedingly small 
proportion in the secretions. 

I have said in the last lecture that sulphuretted hydrogen 
passes in part unaltered ; it may be collected in the respiratory 
exhalations; there is, however, a certain proportion which passes 
into the state of sulphurous acid. But the sulphides of potassium 
and sodium are burned in much larger proportion. 

There is also a general rule, discovered by Chevreul, applied 
by Woehler, and of which examples are known in therapeutics 
and hygiene, that is, that the presence of an alkali aids in com- 
bustion. Consequently an acid, which is not burned when free, 
will be more apt to undergo combustion if in combination with 
an alkaline base ; thus, the sulphide of potassium burns with greater 
facility than sulphuretted hydrogen, and passes to the state of 
sulphate of potash. • 

The organic acids, when they are in the free state, burn some- 



356 PRINCIPLES AND METHODS OF THERAPEUTICS. 

what, but imperfectly, and very slowly. On the contrary— as 
Woehler has demonstrated, and Mialhe has established by new 
facts — when these same vegetable acids are combined with alkaline 
bases, even with lime, but particularly with soda and potassa, 
they are consumed with extreme facility, are transformed into 
carbonic acid and water,, and then, instead of the citrate or tartrate 
of potassa and soda in the urine, are found carbonate of potassa 
or soda. This explains the modus operandi in treatment by 
grapes, cherries and strawberries ; these fruits have an identical 
action, in rendering the humors alkaline, with bicarbonate of 
soda or the treatment by Vichy and Vals mineral waters. 
These substances are almost completely, it may be said completely 
consumed, for they are never found in the state of citric or malic 
acids; but they a»e consumed slowly, more slowly for the last 
acids 1 have mentioned than for the first. The acid they most 
rapidly consume is the one normally present in greatest propor- 
tion, acetic acid ; then comes citric acid and malic ; but oxalic acid 
is consumed much more slowly, for it forms in the emunctories 
almost insoluble combinations with lime, from which results a 
state of inalterability not acquired by the other acids. Such, 
then, is the order in which these substances are consumed. 

I shall now present to you a fact of the same order, con- 
cerning those powerful alterative substances which cause modifi- 
cations through their nature alone. While tartrate of potash is 
consumed with so much facility that it is collected almost in total- 
ity as carbonate, on the contrary, it is found that the double tar- 
trate of potash and nickel does not suffer combustion. The nickel 
prevents the combustion of the tartaric acid, even though it be 
partly combined with the potash. It is well to be acquainted 
with these facts, because they will certainly aid when the general 
laws are taken into consideration, in the comprehension of many 
processes which yet remain obscure. 

But these two categories of substances, of which one series is 
partly consumed, and the others burned almost completely, 
form in reality but one species ; combustion being established 
with greater facility in one series than in the other ; there is no 



ELIMINATION OF MEDICAMENTS. 357 

fundamental difference, and a substance of the first series can be 
placed in the second, and vice versa, where we suppose that com- 
bustions are imperfect, by simply varying the doses introduced 
into the system. Take, for instance, alcohol, of which I have 
already spoken, but on which I wish to insist. This is a very 
interesting question, on which many dissertations, have been 
made ; a very profound discrepancy exists between the different 
observers on the question, as to what becomes of alcohol intro- 
duced into the system. Certain observers, as you know, say that 
alcohol is a combustible aliment, aiding in respiration ; that it 
enters into combination with all the ternary substances intro- 
duced "as aliments, that is with the fatty and saccharine matters, 
which are assuredly the best substances for inducing combustion. 
Others, on the contrary, assert that alcohol passes without altera- 
tion ; we have been able, they say, to collect it in the secretions. 

Both positions are, as I have said, correct. The opinion of 
the first series of observers is correct for the remedial, physio- 
logical, or hygienic use of alcohol ; the others say what is true 
when the substance is taken in actual toxic doses. 

Thus, I have said to you, when a large quantity of alcohol is 
introduced, it passes, in great part, unaltered in the secretions, it 
is immediately found in the state of aldehyde. 

On the contrary, where alcohol is introduced in very small 
quantity, in hygienic or physiological doses, it undergoes combus- 
tion sufficiently to become, probably, water and carbonic acid. 

Consequently, as you see, the same substance may be placed in 
either or both of the two categories. The quantity of the active 
principle found in the secretions shows, then, only the difference 
between what has been introduced and what has been destroyed. 
And this difference varies necessarily in accordance with the con- 
ditions we have indicated ; the combustibility, more or less 
marked, of the substance and its alterability ; there are certain 
substances of which but a very small proportion is found in the 
urine, while of others ninety per cent, may be collected ; such 
are the chlorate of potash and the sulphate of quinine, but this 
last, with the reservation I have made concerning it. Then there 



358 PRINCIPLES AND METHODS OF THEEAPEUTICS. 

are all the intermediary substances between these two extremes, 
of substances of which almost nothing is passed, and others of 
which almost the totality is found in the secretions. When these 
substances are examined as they pass in the secretions, it will be 
perceived that the principal changes they have suffered have been 
brought about by oxygen ; they are oxidized ; the others have 
entered into new organo-metallic combinations. 

I have cited to you examples, many of which are familiar ; 
substances which, introduced as hydrogenized carbons, or some- 
thing similar, generally ternary substances, contract combinations 
with nitrogenized animal principles, which are in reality the 
waste matters ■ thrown off by the tissues, with glycocol particu- 
larly ; forming new combinations much more stable than a great 
number of the waste materials from which they were formed. 
And these new combinations thus formed carry off with greater 
facility, and become means of excretion for the peccant matter 
contained in the economy when it is saturated with principles 
not completely consumed, and which could not pass out. 

Thus the first example of this kind is benzoic acid. It has 
been seen that it is transformed into hippuric acid. We know 
that this change results from the combination of the benzoic acid 
with glycocol. These facts are numerous, and it might be said 
that all the hydrogenized carbons, which are called essential oils, 
as those of turpentine and eucalyptus, are transformed partly 
into acids resembling hippuric acid. They are seen to pass in 
the state of nitrogenized combinations, and are thus rendered 
almost unrecognizable as regards their chemical and organo- 
leptic properties. It is evident to me that these are the substances 
which give a peculiar smell to the secretions ; when a person 
has taken the spirits of turpentine, Canada balsam, essential oil 
of cajuput, or balsam of copaiva, the odor resembles that of 
violets. But the odor of violets is not always obtained ; some- 
times it rather resembles that of melilot, or of vanilla. These 
are evidently acids formed by combination. But again, there are 
substances which are split up before passing in the secretions, 
reduction having taken place. 



ELIMINATION OF MEDICAMENTS. 359 

Finally, there are substances which appear to pass unaltered, 
and which are found almost in totality in the secretions, such as 
quinine, but which, nevertheless, have undergone certain altera- 
tions, difficult, it is true, to demonstrate, but becoming more 
clear when this substance has been introduced into a living or- 
ganism, where it induces none of the symptoms usually produced 
by quinine, that is, where the substance is rendered inert. 

Up to the present we have considered only the nature of the 
effects produced by remedial or toxic agents. But it is important 
also to seek an explanation of the circumstances which cause 
variation in the physiological and remedial effects. There are 
two principal causes for these variations of action : the first is 
the power of the agent itself, which varies in different cases and 
under different circumstances; the second is the ensemble of 
phenomena as regards the organism, and which may be expressed 
in one word : resistance of the organism. 

The " peculiar power of a remedial agent " is not an expression 
having always the same significance ; it does not signify that a 
medicament is always endowed with the same virtues and in the 
same degree, and that it can always exercise a calming or stimu- 
lating action. The peculiar properties possessed by the remedial 
agent are not thus in relation with the particular conditions of 
pharmaco-dynamic energy possessed by or inherent to it. 

If we study the action of analogous principles grouped in the 
same substance or in a group of vegetables which act in the same 
way, here is what we observe : If we take alcohol, we remark, 
according to the experiments made by Dujardin-Beaumetz, that 
certain forms of alcohol are endowed with great energy, while 
others are tolerated with facility, and cause much less marked 
symptoms of intoxication than the first kind. Ethylic alcohol is, 
for instance, supported with facility by the human race, while 
amylic alcohol, from potatoes, is very poisonous. 

If we take the poisonous solanacese we again finci a gradual 
descent in physiological action, descending from the strongest 
alkaloids, such as atropia and duboisia, to daturia, nicotine and 
solanine, which is the feeblest. But there are other analogous 



360 PRINCIPLES AND METHODS OF THERAPEUTICS. 

facts. Very notable and often striking difference in intensity 
of pharmaceutic and dynamic action is observed in substances con- 
stituted in the same manner, or which are identical in all essential 
parts to substances which are said to be isomeric. These are 
metallic or metalloid substances which owe to their own peculiar 
nature, independently of their state of combination, their organo- 
leptic qualities, and, consequently, their physiological action ; 
here we find the cause of the modification in intensity of the 
physiological action to be the structure and dynamization of the 
substances. I will give you an example. Oxygen is an agent 
of combustion ; atmospheric oxygen has qualities aiding in com- 
bustion with which you are all acquainted ; it gives us the means 
of burning up our own tissues. But there is one form under 
which oxygen presents itself — allotropic it is termed — formed 
of three condensed molecules of oxygen, a form which presents 
enormous dynamization, so that it becomes a very energetic 
poison, and I have given you an account of some of the symp- 
toms produced by it on myself. 

For isomeric substances there are also great differences in 
intensity of action, such, I repeat, that it is not sufficient to know 
that the substances are isomeric to admit any identity of physio- 
logical action. No identity of action must be thought of before 
having really observed such identity. I have already spoken 
concerning the difference in action of the glucose of diabetes and 
that of grapes. Take, for instance, the isomeric substances 
obtained from quinquina; the same fact holds true; on one hand 
you have quinine, which is of great power ; on the other quinidin 
and quinicin, which are inert. Again, cinchonidia is almost the 
equal, perhaps the equal of quinine, although there are not 
sufficient experiments to decide the question; while on the other 
hand, cinchonine and cinchonidine are inert. These substances 
are isomeric, but the molecular arrangement is different. In the 
series of caffeins, there are great differences between the caffein 
obtained from coffee and that obtained from tea, from the leaves 
of the mate plant, and from Paullinia. Thus, experiments which 
I have lately made show that these substances, which have 



ELIMINATION OF MEDICAMENTS. 361 

exactly the same composition, which for the chemist are identical, 
are substances which act differently. Tims, guaranine is much 
more active as a diuretic than thein or matein. Consequently, 
as you see here, again, in this group, it is necessary to take into 
account structure and dynamization of the substances, in order 
to explain their effects. 

There are conditions of another order which explain the ac- 
tivity of remedial substances, their state of mechanical division, 
their state when about being formed, or nascent state, and 
finally whether they are in the free or combined condition. It is 
clear that it is not the same thing for a substance to be in com- 
bination as for it to be free to penetrate into the combinations 
which are offered to it when it arrives in the interior of the 
organism. 

For instance, I will cite to you these facts : Sulphur is found 
in pharmacy, under two principal forms; the first is sublimed 
sulphur, washed or not; the second is precipitated sulphur, 
called milk of sulphur. Sublimed sulphur is dissolved with 
less facility ; the other presents itself under the form of an impal- 
pable powder, of pale yellowish color; it is almost white. But 
this last variety dissolves better, and consequently penetrates 
with more facility, by absorption, into the economy. 

Arsenic is generally combined with oxygen, in arsenious 
acid, or combined with a base, as arseniate of potash or soda; 
these substances have greater activity than their conditions of 
solubility would lead us to suppose. 

On the contrary, I have shown you, by a curious example, 
almost impossible of comprehension, that cacodylic acid, formed 
by methyl, in which a certain proportion of hydrogen is replaced 
by arsenic, and which contains fifty- four per cent, of arsenic, pro- 
duces no effect on the digestive tube, and has hardly any poisonous 
action. It is probable that this is due to the very great resistance this 
substance offers to absorption, and I will shortly show you that 
analogous effects are obtained in a somewhat different manner by 
simply incorporating substances in inert matter. Besides the 
composition of the active substance, there is also the question of 



362 PRINCIPLES AND METHODS OF THERAPEUTICS. 

quantity. It is easy to understand, and every one considers it as 
a fact to be taken for granted, that the intensity of the 
action of a remedial agent is in proportion to the dose given. 
But it is necessary to be reserved as regards this point, and I will 
cite examples where it would seem that the intensity of action 
was in inverse proportion to the dose. It is right for me to 
warn you that it is not the dose introduced at any one time, to be 
absorbed, that requires careful consideration, nor the quantity 
that may have passed through the organism, and which may be 
very large if introduced during a long period ; what is of para- 
mount importance is the quantity present at any one time in the 
circulation and in the parenchyma, and which consequently is in 
the state to act. 

I agree with every one, what might, for that matter, be pre- 
sumed in advance, that there is a direct proportion between the 
quantity of the active substance introduced into the primse via? 
and the effect it produces, with the condition that this substance 
be in favorable condition to act; but you will see that these 
conditions are not always realized, and this fact should receive 
careful attention when it is desired to explain the greater or less 
activity of substances from a certain dose. Consider, for in- 
stance, the solubility, which has great influence ; the same sub- 
stance may, as it is introduced in a soluble or insoluble state, 
produce no effects, or, on the other hand, act with great energy. 
Kermes and magnesia are in this category. For magnesia, it 
is easy to understand why this is so, for it does not act of itself; 
it is necessary that it be dissolved, that it become carbonate of 
magnesia, with excess of acid, in order to become active in 
any degree ; generally it is transformed into acetate or into 
other salts, through the presence of acids of more or less 
energy. 

Kermes (sulphuret of antimony) is somewhat less known. 
Physicians are often disappointed with an excellent preparation 
of kermes ; they obtain effects so variable that many no longer 
use it. Kermes will act with great energy if you introduce an 
acid concurrently with it. If you administer it to a patient in 



ELIMINATION OF MEDICAMENTS. 363 

pneumonia, or in capillary bronchitis, and thoracic affections of 
gravity, kermes, given simply with a little gum water or any 
mucilaginous water, if there is no acid in the primse vise, will 
pass almost unperceived. If, on the contrary, you give at the 
same time some lemonade, or somewhat new wine, then the 
kermes will have considerable effect; even with no very con- 
siderable doses you will have effects approaching those of 
tartar emetic. Calomel presents analogous peculiarities. In 
general, it may be said, that when the conditions are favorable 
to absorption, the effects are considerable, while under con- 
trary conditions they are insignificant or, at least, considerably 
enfeebled. 

We will consider the conditions which render remedial agents 
more or less active under other circumstances. It is a ques- 
tion which will present itself to you, whether a solution should 
be made dilute or concentrated to render it more active ; certain 
general rules may be traced. -It may be said that a solution 
passably concentrated is absorbed quicker, penetrates with greater 
rapidity, produces more considerable effects ; while a solution too 
much diluted produces but feeble effects. 

But certain remarks should be made on this rule. If the 
solution is too concentrated and contains a substance capable of 
exercising considerable local action, it is clear that in such case 
absorption, instead of being increased, will become slower. You 
employ tannin to arrest hemorrhage ; it must be prescribed in 
the solid state ; we are obliged thus to have recourse to it ; but 
after having introduced it in the solid form it is necessary to 
immediately give water to dilute the tannin, because if tannin 
in the solid state comes in contact with the mucous membrane, 
so much corrugation is produced that there results almost total 
impossibility of absorption. It is the same with the ferric salts. 

There are other circumstances where the general action is pre- 
vented by a too energetic local action. For instance, it is useful, 
in a certain number of cases, to introduce neutral salts into the 
economy. Among other diseases, when albuminuria is present 
conjoined with a state of dyscrasia, you can give with benefit not 



364 PRINCIPLES AND METHODS OF THERAPEUTICS. 

only sea salt, but also you can give — and thus aim, at once, at a 
local treatment and impress the constitution of the patient — 
mineral waters containing large proportions of neutral salts ; for 
instance, you may give Friederich shall water. I have given it 
for a long time, knowing that it contains much chloride of sodium 
and sulphate of soda, to patients affected with albuminuria, 
through some general morbid state, and I obtained good results. 
Better still, the waters, which I have called mineral lymphs, 
because they contain all the salts present in the blood, can be 
administered, as the waters of St. Nectaire and Royat, which 
may thus be given to improve the condition of the serum of the 
blood. 

If you give too large a quantity of these waters you will induce 
purgation. In this event a very small proportion enters the 
system, although a small quantity enters, for we know, to-day, 
that even in giving the most energetic purgatives there is always 
some slight absorption. But the greater the hypersecretion, the 
less proportion enters by absorption. There are circumstances 
in which the administration of these substances should not be 
pushed. 

There are also cases when too much dilution injures the effect 
produced by diffusion. If you desire an example I will com- 
pare pure alcoholic liquors with the same when diluted with 
water. If you say to one to whom you recommend sobriety, 
a You are gouty, if you take wine in the pure state, it is bad for 
you," he will reply: "Doctor, I take no more alcohol than 
you do; you add much water, I take my wine pure, but in the 
end it amounts to the same." No ; when wine or liquors are 
taken pure, the absorption of the small doses is effected with 
great rapidity, since all passes and there arrives too great a pro- 
portion of alcohol at one time in the blood. On the con- 
trary, where but a fourth part of wine to a glass of water 
is used, after three or four glasses have been drunk, but one 
entire glass of pure wine has been taken ; and it thus penetrates 
very slowly, and you have never those violent effects determined 
by a small quantity of alcohol in an almost pure state, those more 



ELIMINATION OF MEDICAMENTS. 365 

or less durable symptoms of stimulation, which prove so danger- 
ous in heart disease and in gouty affections. You see, conse- 
quently, that there are great differences in action with the same 
doses employed. Again, when you wish to obtain powerful effects 
from an active substance, such as quinine, you will not give it at 
long intervals, for there would never be at any one time but a 
small proportion of quinine in the blood, and one dose would 
always have sufficient time for its action before the second 
would arrive; so that there would never be any accumulation of 
doses, and, consequently, no accumulation of action, for it maybe 
said that the one brings about the other, under conditions which 
are alike. 

These, then, are conditions it is important to be acquainted 
with. The others which I have spoken to you of are: the 
degree of division, and the more or less solubility; another, and 
often artificial condition, is the covering or preparation of 
remedies. In the pharmacies it is the custom to incorporate 
active substances with others more or less inert, which are 
added to aid in their action or obviate too active effect. 
This disguising medicament, which is often not considered as 
such, because it is often imagined that true combinations are made, 
presents more or less obstacle to the activity of the drug, because 
it opposes its absorption. And in a certain number of cases there 
is immense difference between the activity of a substance when 
given pure or in solution, and when given in a divided state, 
mixed in with an inert substance. 

Take, for instance, iodine in the state of a metalloid ; it is 
caustic ; it would certainly cause suffering, inflammation, even 
ulceration, to let fall five centigrams of it into the stomach. But 
forty centigrams of the iodide of starch, containing four centi- 
grams of iodine, may be introduced; and while five centigrams 
sufficed to produce the disorders I have mentioned, this dose of 
iodide of starch has no effect, either local or general. How can 
this be explained? First, what is known as iodide of starch is 
not in reality iodide of starch ; the iodine is simply incorporated 
in the interstices offered by the layers of the starch granules, 



366 PRINCIPLES AND METHODS OF THERAPEUTICS. 

between which the iodine is present in a state of extreme division ; 
this state of division is the same when introduced into these inter- 
stices as when iodine is observed on the internal surface of a 
bottle in which a few drops of the tincture have been shaken up 
with more or less force. Under these conditions iodine is blue, 
and it is on this account that iodide of starch is blue. 

The reunion of these two circumstances — disguising in inert 
matter on one hand, and extreme state of division on the other — 
cause, then, considerable difference in the mode of action of dif- 
ferent remedial agents ; so much so, that many preparations 
which unite both these unfavorable conditions, to wit, first, 
a very coherent substance, difficult to act on, either by the 
liquids of the economy or by substances capable of acting through 
their affinities, such as the alkalies or acids ; and again, this sub- 
stance being disguised in foreign matter, and the entire mass 
silver-coated, have no action whatever. It will happen to 
you, from time to time, to administer to patients affected with 
catarrh of the urinary passages prepared turpentine, con- 
sidering that in this way you will have all the advantages and 
none of the inconveniences of the medicament. When these 
pills are very hard, and well enveloped in a pretty sheet of 
silver, they pass completely unaltered ; they become perpetual 
pills, as it were. 

I have observed this same phenomenon occur with pills of 
resin of copaiva. I bought from the perfumers resin of copaiva 
from which they had extracted the essential oil to augment the 
strength of their various perfumes, and I employed it. I per- 
ceived, at first, that I obtained no result, because the pills passed 
unaltered. I then associated the resin of copaiva with a substance 
capable of dissolving it, and I obtained good results. You see 
that the knowledge of this is of practical interest. 

I have just shown you that the intensity of the effects pro- 
duced is not always in proportion to the quantity of the substance 
employed ; that it is necessary that the substance you confide to 
the digestive organs be of such nature and under such conditions 
as to be easily absorbed, and with brief delay, so that it may be 



ELIMINATION OF MEDICAMENTS. 367 

retained at one time in sufficiently considerable quantity and 
in the right proportion to be efficacious. 

There are, as I have said, some circumstances entirely para- 
doxical under which medicaments act least when introduced in 
most considerable quantity. This would seem favorable to in- 
finitesimal doses. But no: you will see that this circumstance 
can be explained with facility. Here is an instance. You are all 
acquainted with the antiplastic action of calomel; you know that 
in a greater degree than the other mercurials, it affects the sali- 
vary glands, and that stomatitis is, alas, too frequently induced, 
even by small doses. Thus, when it is desired to produce 
salivation, it is given in divided and very small doses frequently 
repeated. In this way, if ten or twenty centigrams are adminis- 
tered during the course of the day, stomatitis may be induced in 
twenty-four hours. It would seem, after that, that it would be 
very dangerous to introduce large doses of calomel. ~No : with 
large doses, no similar effect is produced ; it may be that solely 
cholagogue effects are induced, and no effect at the commence- 
ment of the digestive tube ; that all the effects, in a word, are felt 
in the liver. Finally, when enormous doses are employed, no 
effect at all is produced. 

Thus, in India, where physicians employ large doses of calomel 
to combat a great number of affections (particularly in former 
times, to-day they have somewhat modified their therapeutics), 
such as chronic diarrhoeas and dysenteries, often four, five 
and six grams of calomel were administered, which, instead of in- 
creasing the diarrhoea, caused its cessation. 

Is this homoeopathy (similia similibus curantur) ? Ko : this 
simply shows that when the physicians in India gave consider- 
able doses of calomel, there was no possibility even of its partial 
transformation; the enormous dose surrounded all the substances 
capable of rendering calomel soluble, and the drug thus passed 
through the intestines acting as an absorbing substance. This 
fact is even more evident for oxide of zinc ; with small doses, it 
has nauseating and emetic effects ; large doses, absorbing effects. 
It is excellent to arrest diarrhoea. Why? When you give 



368 PRINCIPLES AND METHODS OF THERAPEUTICS. 

little, there is sufficient acid to form lactate and chloride of 
zinc ; when a large quantity is given, a salt so basic results that 
it is no longer a soluble product, and the zinc passes, producing 
simply the effects of a chemical absorbent. You see that these 
facts merit being remembered by you. 



ACCUMULATION OF REMEDIAL AGENTS. 369 



CHAPTER XXIX. 
Accumulation of Remedial Agents. 

Insignificance of small doses. Therapeutic minimum ; tolerance and in- 
tolerance. State of the organs of absorption ; individual conditions ; state 
of the secretions. 



Gentlemen : 

I follow up the enumeration of conditions which cause varia- 
tions in the actions of medicaments by speaking to you of the 
insignificant action of small doses. It might be thought that 
if a substance has an action which might be expressed by 10 
at a certain dose, that with a dose ten times smaller its action 
might be expressed by 1. The facts do not confirm this sup- 
position. There is a minimum dose under which the substance no 
longer acts, and it passes, it might be said, unperceived. For in- 
stance, you may give a milligram of tartar emetic without induc- 
ing nausea or vomiting, unless the phenomenon of accumulation 
of doses, of which we shall shortly speak, is produced. In the 
same way you can give a gram of castor oil without purging, and 
that every day in the year. And yet, you will have given dur- 
ing the year 365 grams of castor oil; but there never has been 
enough at any time in the organism to produce sensible effects. 

This fact, verified with facility for castor oil, exists also for 
other medicaments, of which the action is less visible. Effica- 
cious doses are needed, as I have written long ago in " Trousseau's 
Therapeutics ;" under these doses no effects are produced. Another 
reservation to make in regard to the proportion of doses is this : 
not only the effects may not be in proportion to the dose, but it 
will be observed that when the dose is gradually increased there is 
a change in the effects produced. I cite as an instance, opium or 
morphine. With small doses there are excitation and drunken- 



370 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ness, stimulation ; so much so that the eastern nations seek this 
stimulation and often go to combat after having taken a small 
dose of opium. But a relatively feeble dose of opium is required 
to produce a stimulation of the circulation analogous to that pro- 
duced by alcohol. On the contrary, with a somewhat more 
elevated dose, you will have those phenomena of cerebral conges- 
tion which render opium the most powerful of hypnotics acl of 
stupefying agents affecting the sensory nervous system. What 
happens for opium in more or less elevated doses, and on the other 
hand, in feeble doses, of which I have spoken, happens also for 
digitalis, which produces entirely different effects when the dose is 
moderate from those observed when the doses are excessive and 
beyond the usual quantity. With moderate doses the pulse be- 
comes slower, each pulsation augmenting in force, the peripheral 
circulation being accomplished with the more activity that the 
cardiac revolutions are less numerous ; but on the contrary, the 
tension augments when the dose has been further augmented. 
The dose may not be too large when a single dose is intro- 
duced, but on account of the accumulation apt to occur, toxical 
phenomena will be observed. The pulse is at first accelerated, 
and while with moderate doses it underwent a change favor- 
able for the circulation, becoming slower, with over doses the 
circulation becomes embarrassed, the pulse becomes irregular 
and insensible, in short, toxical phenomena result. You have 
at the same time all the phenomena of intolerance well known in 
the history of digitalis. Consequently, as you see, not only the 
physiological effects are not always increased by increase of the 
dose, but often the action is modified. 

We have just seen what influence the dose has on the thera- 
peutic power of a drug, with all the reservations necessary as 
regards the comprehension of facts in appearance paradoxical. 
I have spoken to you, also, of the influence of all the physical 
and chemical circumstances existing in remedies, and which may 
modify their conditions of solubility. 

It is necessary, now, to consider what influences, on the part 
of the subject who ingests medicaments, modify their activity. 



ACCUMULATION OP REMEDIAL AGENTS. 371 

There exist, on the part of the patient, conditions sometimes 
eminently favorable, in other cases very unfavorable. As to the 
action of remedial agents, it is necessary to be acquainted with 
them and have their effects in consideration in prescribing, for 
you will be obliged, according to circumstances, to take certain 
precautions in order to cause the remedies to be accepted by the 
economy and to assure their effects. I will pass in review, one 
after the other, the state of the organs and the functions — activity, 
inertia, the natural or acquired effect of impressions on the 
patient, the state as regards tolerance and intolerance. 

I will say a few words on age, sex and race, for there are 
considerable differences observed in the manner races are affected 
by medicaments, and this is not the least interesting part of our 
subject. In the first place, as regards the organs of absorption, 
we find here considerations of vascular tension, which are of 
extreme importance, and you will see that in ancient practice 
the importance of these conditions was understood when science 
was less advanced. Sometimes tension is active ; at other 
periods tension is passive. 

Is there any necessity of defining these terms? Yes; for con- 
siderable confusion exists, and generally two phenomena, distinct 
from each other, and often opposed one to the other, are con- 
founded. 

Passive tension is represented when one finger is com- 
pressed between two others, since by this process all the blood 
in the finger is forced toward its extremity, and maintained 
there ; this kind of tension is confounded with active tension, 
which consists in this : not only is there considerable force of 
propulsion on the part of the central organ of circulation, but 
there is considerable energy of contractile power in the entire 
vascular system. With these two conditions, great force of pro- 
pulsion with considerable contraction, you will have what is 
termed elevated tension. It is this state alone to which attention 
is generally attracted ; but, nevertheless, there are cases where 
the tension is purely passive, resulting from a diminution in the 
contractility of the vessels. It is passive from this point of view, 



372 PRINCIPLES AND METHODS OF THERAPEUTICS. 

but is, nevertheless, the result of some change taking place since 
the vessels have lost their tonicity. This passive tension is aug- 
mented under the influence of the absorption of a large quantity 
of liquid, or when such is present in the blood. This is what 
happens in true aqueous plethora, or when the blood is very 
abundant. We can have this state of veritable plethora under 
peculiar and various conditions, as has been pointed out by 
Magendie ; thus a sort of conditional and necessary plethora ex- 
ists momentarily after a repast, where a large quantity of aliments 
and liquids have been ingested ; and you will observe consider- 
able variations as regards this state of aqueous plethora, accord- 
ing as the subject has or has not just been ingesting fluids. This 
is so true, that the day after a general or local bleeding, after- 
having the day previously noted the absence of any murmur in 
the vessels of the neck, it will be found that when the patient 
has taken liquids, introducing water to replace the blood lost, 
a fine bruit, due to the anaemic state and the hydremic con- 
dition of the blood, can be heard ; a double murmur, the true 
bruit du diable.* 

You can see, then, that when a large quantity of blood has 
been taken from the system there is no murmur ; this murmur is 
perceived only after the loss has been repaired by the ingestion 
of liquids. There are also states of localized passive tension which 
result from mechanical obstacles being opposed to the venous cir- 
culation, as in cases where the blood in the veins mounting almost 
perpendicularly, there is more or less stasis through compression 
of an important vein. In this case of venous stasis there is diffi- 
culty in the introduction of medicaments by the cutaneous 
surfaces. There are also cases in which a state of active hyper- 
emia, a veritable state of more or less intense phlogosis, some- 
times of plastic variety, opposes obstacles to absorption. Every 
body knows that when inflammation exists the inflamed surface 
is little apt to absorb the active substance deposited on its surface. 

* The souffle found in the vessels of the neck in aneemia is called in France 
" bruit du diable," from the supposed resemblance between it and the sound 
produced by a child's plaything called "le diable." 



ACCUMULATION OF REMEDIAL AGENTS. 373 

There are a variety of practical applications to be made 
of this fact — that absorption is diminished under the in- 
fluence of a state of exaggerated passive tension. This should 
show you that when you wish to have as rapid absorption as 
possible, the medicaments should not be administered when the 
stomach is full, or when there is plethora, determined by a large 
meal. 

There is another well known circumstance : that is, when it is 
desired to prevent absorption, an artificial obstacle to" the return 
of the venous blood may be created. When a person has been 
stung or bitten by an animal, it is, of course, of benefit to 
cauterize, but a caustic substance is not always at hand, while 
compression -can be made with great facility while waiting until 
a caustic can be procured, to afford the subject protection against 
ulterior accidents. This will suggest to you that when you wish 
to render a cutaneous surface prepared by a blister more capable 
of absorption, it must be so arranged that this blistered surface 
be not in an inflammatory state at the time of the application. 
Thus, it has been observed that when a vesicated surface is very 
much inflamed it absorbs very little, and that even large doses 
of morphine have no effect on the general system. And there 
is another sequence to be drawn from these considerations : when 
you have to deal with a plethoric subject presenting a state of 
hyperemia of various organs — a large liver, such as gouty indi- 
viduals or those who live somewhat too highly — it is necessary 
to commence treatment by depletion. If you do not commence 
by emptying, as it were, your patient, you will obtain almost 
nothing from medicaments. Thus, it is very often necessary to 
give an emeto-cathartic to a patient in rheumatism, whom yon 
may wish to submit to the influence either of sulphate of quinine, 
or of any other substance which must be absorbed. You will 
do the same when, in the course of a disease of the heart, you 
wish to employ digitalis or the diuretics. 

When you have, then, to deal with men overstocked with 
blood, commence, I repeat, by depletion. It is only when you 
have, as it were, made room, that you can with utility commence 



374: PRINCIPLES AND METHODS OF THERAPEUTICS. 

to prescribe digitalis. It is the same with the sudorifics : they 
do not act in subjects whose systems contain too large a propor- 
tion of liquid materials. 

When you make use of the anaplastics, you should use mer- 
cury for its purgative effects, before attempting to obtain the other 
virtues it possesses. Suppose you have to deal with a malady 
such as psoriasis. If you wish to give mercury it will be neces- 
sary first to purge the patient several times. And with even 
greater reason when it is wished to induce the resolution of mor- 
bid swellings, etc. ; it is clear that in such a case it is necessary to 
commence by removing from the tissues all the materials which 
usually oppose obstacles to the resolvent action of iodide of 
potassium, and of like medicaments. 

In cases where the active tension is augmented, almost the 
opposite rules to those of which we have spoken would be applied. 
If you have very marked active tension, and at the same time an 
empty state of the meshes of cellular tissue, then you have the 
circumstances most favorable to absorption, and consequently to 
remedial action. It is the exact opposite of the state we have just 
been considering. This is so true, the knowledge of these facts 
is so ancient, that among all people you will find in vogue 
practices which consist in diminishing this active tension, dimin- 
ishing this vascular rigidity, and attempting to bring about the 
condition of passive tension of which I have just shown you the 
inconveniences. 

For instance, when a negro in the Antilles or Senegal is bit- 
ten by a venomous serpent, he is submitted, as a matter of course, 
to alcohol in very large doses, while at the same time sudorifics 
are given. He is made drunk, and left dead drunk, when it is 
wished to prevent him from dying from the action of a poison 
such as that of the crotalus or trigonocephalus. Why this prac- 
tice? Because during this powerful action of alcohol there is, 
as you know, universal congestive tension. These individuals 
have all the tissues congested, and while in the state of general 
hyperemia they do not absorb, and consequently they escape the 
mortal, or very noxious effects of the poison; for the poison, just 



ACCUMULATION OF REMEDIAL AGENTS. 375 

as for the medicaments, what makes the activity is the quantity 
at any one moment present in the economy, and which may thus 
act all at once, either on the nervous system or on the heart. You 
see, then, that there are certain popular practices which show us 
how, with the aid of instinct alone, the existence of certain phy- 
siological conditions have been divined which science has not 
discovered until later. 

There are also some chemical conditions of the cavities in 
which absorption should take place, which cause variations in the 
activity, and hence in the physiological and remedial effects of 
medicaments. 

We know that the presence of acids, of alkalies, of albuminoid 
substances, and of fatty matters, is, if not indispensable, at least 
of use in aiding the absorption of a large number of medica- 
ments of themselves rather difficult of dissolution. It suffices 
to know this general law — the necessity of the presence of modi- 
fying substances — to understand that, according as they are in 
abundance, in small proportion, or not at all present, there will 
be facility or difficulty of absorption, or no absorption at all. 
Thus the acidity of the stomach will favor the introduction of 
all the substances which are in need of acid to penetrate into the 
economy ; such as the metals and very insoluble acid salts. And 
thus, again, the opposite condition will prevent absorption. Al- 
kalinity of the intestine is favorable to the absorption of a cer- 
tain number of substances, and in particular, of arsenious acid, 
as also of salts having an alkaline or an earthy base, and which 
have acids rendering them insoluble. Thus the tartrates and 
the oxalates of lime, of potash and soda, are little soluble when 
they are acid, but if they are easily soluble then they are alka- 
line and basic. Consequently, they can penetrate with more 
facility when the amount of alkali which they meet with in the 
intestine is more considerable. 

We may say the same of alkaline chlorides, albuminoid 
principles and fatty matters, which aid in the introduction of 
certain metallic substances, soluble in albuminoid principles ; or 
of phosphorus and sulphur solution in fatty matters. 



376 PRINCIPLES AND METHODS OF THERAPEUTICS, 

When food too much salted is taken at the same time with a 
large dose of calomel, marked poisoning may result by the for- 
mation of a very poisonous double chloride. The chloride of 
sodium may also have accumulated (from articles of food 
containing a too large proportion of salt), before the introduction 
of the medicament. It is clear that you will not obtain the same 
effects among patients entirely deprived of salt, as during the 
siege of a city. It is the same for albuminoid principles ; they 
are first favorable to the dissolution, then to the absorption, of 
substances rendered soluble by them. 

Some conditions peculiar to individuals are without great 
importance — the rapidity of the circulation, the speed with 
which the substances penetrate into the tissues. But there are 
other conditions of real and great importance. Such is the 
rapidity of molecular change; this has great influence upon 
the physiological action of substances which are about to take 
part in tissue formation, as the renovation is, on this account, 
made with more or less rapidity. There is also the rapidity 
with which the substances are destroyed; for the important 
point is, not how large a quantity has been introduced, or which 
has been circulating in the blood, but the quantity which is 
present in a state to act at any one moment on the system. It 
can be easily understood that if a substance is introduced, even 
in large quantity, and is destroyed with extreme facility, there is 
never sufficient present to produce remedial or toxic effects. 

Another condition of weight, as modifying the intensity of 
physiological action, is the state of the secretions. 

If the salivary, biliary, and in. particular, the urinary secre- 
tions are very active, when, consequently, there is great rapidity 
of excretion, there will be great difficulty in producing any 
considerable remedial effect, and in order to obtain such it will 
be necessary to prescribe very large doses. If this condition is 
excellent in a certain number of cases where it is desired to 
eliminate a poison, it is unfortunate in others, where it is desirable 
to produce remedial effects. If the secretions are in a languid 
state or completely dried up, a parched mouth, with anuria or 



ACCUMULATION OF REMEDIAL AGENTS. 377 

oliguria, under these conditions even small doses of active sub- 
stances will produce considerable effect, and you must be guarded 
in administering remedies. When, then, you wish to introduce 
medicaments of great energy, particularly in subjects requiring 
more circumspection than others, such, as gouty individuals, for 
instance, it will be prudent to inform yourself if they pass much 
urine or but little. If the kidneys secrete abundantly you may 
give colchicum and every kind of active substance, without any 
fear of going beyond the usual therapeutic limits ; if, on the con- 
trary, the urine is scanty, if but five hundred or six hundred 
grams are excreted in twenty-four hours, be on your guard ; give 
but feeble doses, because accumulation might take place, and you 
would go much beyond the therapeutic dose. It is in such 
cases that accidents, often formidable, are induced through the 
influence of moderate doses. You see that it is indispensable 
to take into account these conditions of elimination and secretion. 
It is through such influences that quite a number of substances 
which we employ are sometimes tolerated and sometimes produce 
toxic effects, as sulphate of quinine, which, if it accumulates, may 
be followed by such results as troubles of vision, noises in the ears, 
and deafness, which may persist for months and often for years, 
and which may become incurable ; yet, in other cases, and even 
with large doses, this same drug may determine none of these 
symptoms, or, at least, not sufficiently to be disagreeable. You 
will have but a slight quinic intoxication, and no dangerous 
symptoms. The difference lies in the fact that in the first case 
the secretions were not well performed, the urine was scanty, 
while in the second this secretion was abundant. 

It is the same for salicylic acid, which sometimes leads to 
grave accidents, death even, and at other times is perfectly tol- 
erated. This is because in the former case it came in contact with 
a very irritable kidney, and brought on oliguria and even anuria, 
while on the other hand, in certain subjects, it but renders the 
urinary secretion more active. The same is the case with arsenic. 
I have shown you that the intensity of the action of arsenic 
should not be judged from the dose alone, but also from the 



quantity which might be retained. If it is eliminated, it is noth- 
ing; if on the contrary it is retained, even when but a small 
quantity enters, the result may be very grave. In pathology 
you will find similar facts: How does it happen' that with ad- 
vanced lesions of the kidney there are patients living who ap- 
pear to be in good health, and have never any symptoms of 
uraemia? This happens because they pass a large quantity of 
urine. But it must not be thought that they pass one or two 
litres (quarts) of urine per diem; they pass three, six or eight 
litres in the twenty-four hours. I have even now, in my service, 
a patient presenting this phenomenon, and who, on account of 
the large quantity of urine passed in the twenty-four hours, has 
never had a symptom of uraemia. Suppose the opposite condi- 
tion; the filter is more or less clogged up; you will then see ap- 
pear all the evidences of uraemia, with the well known symp- 
toms which it presents. To sum up, the union of these two 
conditions — on one hand facile absorption, and difficult excretion, 
on the other difficult absorption and rapid excretion — induce en- 
entirely opposite phenomena; in the first case there will be 
considerable augmentation of all the effects, physiological, and 
sometimes toxic, produced by the substance introduced, while in 
the other case a compensation is established between what enters 
and what is excreted, between the exportations and the import- 
ations; there are no symptoms produced and no toxic effect. 

I will now speak to you of a question exceedingly interesting 
from many points of view ; in the first place/by the symptoms pro- 
duced, and again, from its practical applications : I refer to the 
accumulation of medicaments. This accumulation comprises two 
series of facts which differ less than is generally supposed ; accu- 
mulation of action, and accumulation of doses. We will first 
speak of the accumulation of doses; it is the part most easily 
understood, and which also causes the most dangerous results. 
This accumulation of doses consists in this : it is an aggregation 
or collection in the prima? vise of the substances introduced, and 
which, instead of traversing the membranes open to them, remain 



ACCUMULATION OF REMEDIAL AGENTS 379 

there, without being dissolved, without penetrating and without 
acting. There may be two results ; sometimes the substances 
form a sort of metallic mass (gisement metallique), as I have 
called it on another occasion, and this mass remains there with- 
out undergoing any new modification. In other cases, on the 
contrary, it is but a species of reserve, as we will shortly show, 
which is taken up later to penetrate into the circulation. There 
are two conditions under which this accumulation takes place. 
In the first, the accumulation is due to a deficient absorption. 
The substance is soluble as usual, it is sometimes even markedly 
soluble; but what is wanting is the absorbing power of the sur- 
face with which it is in contact, and this defect is met under 
very diverse circumstances. 

What will render this subject most clear is what happens in 
cholera. In this disease you give remedies of decided activity, 
and they produce absolutely no effect ; it is thought that they 
are inert, that it is of no use to have recourse to them. Nothing 
of the kind. This effect is due to another circumstance, as you 
will see; it happens because the medicaments are not dissolved, 
and in other cases, because, though introduced in a state of solu- 
tion, they come in contact with a mucous membrane unfit for 
absorption, because it secretes too much. For you know that 
there is an inverse relation between absorption and secretion. 
If there is enormous hypercrinesis, there is no absorption. 

You may also meet with this defect of absorption produced by 
dessicating substances. Thus, for instance, after the introduction of 
large doses of opium and belladonna into the digestive tube, you 
may observe that certain substances can be introduced with im- 
punity, for they are no longer absorbed. The mucous membrane 
is not only narcotized, it is also in a dry state. 

There are other cases where, the absorbing faculty being intact, 
the substance introduced is covered up in the midst of inert mat- 
ter, hard, and not capable of dissolution. Of course in such cases 
there is no effect, no absorption possible, for it can be effected 
solely on dissolved substances; with, however, the exceptions I 
have already mentioned, that there is sometimes absorption of 



380 PRINCIPLES AND METHODS OF THERAPEUTICS. 

solid substances by a mechanical penetration, analogous to that 
of a blade of grass traversing the polyporus lucid us. 

We have on record cases where pills, of careless manu- 
facture, resisted the diluting and dissolving action of water 
and of the various liquids contained in the prima? vise; I have 
cited to you the case of the perpetual pills, as those of the resins; 
I will cite here pills of more soluble substances, as of the extract 
of opium, but made for a considerable period. The case has been 
reported of a man who succumbed to tetanus, without having 
presented any effect from the opium, which was given in consid- 
erable doses; bat at the post-mortem a collection of opium pills 
was found in the intestine, all intact. This same fact has been 
noted in cholera. The conclusion to be drawn from these facts is 
that opium should always be given in a soluble form. 

There are also substances naturally very insoluble, such as the 
metals, certain metallic salts, certain chlorides (of the metalloids), 
certain acid salts, even those acidified by tartaric acid, which 
may also be accumulated by the same process in the prima? via?, 
through their more or less considerable difficulty of absorption. 
I observed that through whatever mechanism this accumulation 
took place, there are two cases to distinguish. Sometimes the 
substances which have been introduced remain indefinitely in 
the condition of foreign bodies; again they simply form reserves, 
which will be later taken up and become active. 

As an example of the first fact, I will cite the curious bezoars 
(concretions) of magnesia, found so frequently in the intestines of 
horses. Such concretions were also found in the caecum of an 
aged Englishman, who took, every morning, a spoonful of mag- 
nesia; there was not always sufficient chlorhydric, or lactic, or 
carbonic acid present to dissolve it, consequently the magnesia 
accumulated in the part of the intestine where the greatest 
mechanical difficulty to its elimination existed. This bezoar 
stone was as large as the fist. But there is an accident which 
may happen; that is, the substance may be taken up later; this is 
what happens in cholera. 

These same pills of opium, which have been found intact and 



ACCUMULATION OF REMEDIAL AGENTS. 381 

not altered, have in the end been attacked, and here is wna, is 
observed : In the height of the attack large doses of opium 
were given, and without effect, then the symptoms change spon- 
taneously; that is, reaction commences, and with it new conditions 
of the mucous membrane of the digestive organs ; the hypercri- 
nesis is replaced by a somewhat dry state. At this moment 
absorption takes place, the pills are, at least in great part, dissolved, 
and all of a sudden symptoms of opium poisoning supervene. 
This is what has been observed also for pills of nux vomica, of 
strychnine, of phosphide of zinc even. After having obtained no 
result, acute phenomena of poisoning suddenly startle the 
physician. 



382 PKINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XXX. 
Prevention of Accumulation. 

Means o avoid accumulation of doses ; administration in pill form con emned. 
Accumulation of action different from accumulation of doses ; causes and 
variations of accumulation of action. 



Gentlemen . 

To avoid accumulation of doses, the best means is not to em- 
ploy medicaments in the solid state. Pills, particularly when 
well prepared, and enveloped in metallic covering, are bad pre- 
parations. They render service assuredly, for it is the most 
commodious means of administering medicaments, but it is also 
the least secure method, and when you desire the assured and 
prompt action of a remedy, you must not employ pills. 

There is reason, also, to desire the pills made in a certain way; 
a little glycerine favors the dilution of the substance and its 
absorption. But oftenest it will be necessary, when you have 
to deal with serious or grave affections, to have recourse not only 
to soluble substances, but also to substances already dissolved, 
given in the form of syrups and potions, and even in the state of 
very dilute solutions, so as to be sure of giving a dose equiva- 
lent to the effects you wish to produce. These very dilute solu- 
tions render great service ; it is through them that a certain known 
quantity of a substance can be added to a potion. Syrups also 
are useful. 

You know that Trousseau, after having seen how much danger 
there was in giving strychnine in pill form to young patients in 
chorea, finished by prescribing a syrup called after him, and 
which contains sulphate of strychnia. It is certain of produc- 
ing effects, which vary according to the quantity given, and 
according to the state of the subject as regards absorption, but 



PREVENTION OF ACCUMULATION. 383 

effects always in relation with the dose; it gives, consequently, 
excellent results. 

It is desirable, also, to administer well denned substances, and 
which are sufficiently soluble with the aid of certain adjuvants. 
When you employ these substances the modifying agent should 
always be added to the preparation you make use of. I will ex- 
plain : take, for instance, salicylic acid, which is not at all soluble; 
it is necessary to give bicarbonate of soda at the same time with it. 
I take this example, not because I recommend salicylic acid, but 
because this acid being a dangerous substance, on account of its 
topical action, I wish, at least, to spare you the greatest of errors, 
and advise you to employ it in the state of a salt. 

These recommendations which I make concerning this acid, 
I would repeat with even more reason in reference to sulphate of 
quinine, which is soluble, but in small proportion. The acid sul- 
phate is comparatively soluble; it is, then, preferable to attempt the 
transformation of the neutral sulphate into the acid sulphate. 
So that whenever you prescribe sulphate of quinine for your 
patients, it will be desirable to order it in solution, and you will 
be often able to induce even women to take this bitter sulphate 
of quinine, if you will explain to them the advantages of taking 
it in the liquid state. If you administer sulphate of quinine in 
the solid state, and in pretty large doses, as is often required in 
intermittent fever when intense, you will expose yourself, when 
you have given a mass of at least twenty-five or fifty centigrams 
in the solid crystalline state, to produce phenomena of gastric 
irritation, perhaps quite intense, and when these phenomena are 
repeated, to induce a veritable artificial gastritis, which might 
be said to be toxic, and which lasts after the administration of 
the drug has been stopped. If, on the contrary, you arrange it 
so that the dissolution of the sulphate of quinine be aided by 
the ingestion just after the sulphate of an acid solution, lemon- 
ade with citric acid,, for instance, in such case you will be less 
likely to have these inconveniences. 

But you will do better if you first dissolve the sulphate of 
quinine in lime juice; you can, with one tcaspoonful, obtain 



384 PRINCIPLES AND METHODS OF THERAPEUTICS. 

the dissolution of twenty-five centigrams of the salt, and I can 
assure you that this solution is not at all disagreeable for the 
majority of patients, and that it proves of double benefit, inas- 
much as you avoid the disagreeable local effects, and are assured 
of the action of the sulphate of quinine, not only because all is 
introduced, but because it is almost immediately absorbed through 
this state of great solubility. Here, consequently, is an occa- 
sion where you should not fail to accompany the active sub- 
stance with its modifying agent. There are, nevertheless, circum- 
stances which render it impossible to have the substance in such 
a state of solution. You are obliged to use substances which 
become soluble after a length of time, and which, consequently, 
have to be introduced into the primse vise just as we receive 
them from the druggist. Take, for instance, calomel; you cannot 
dissolve it. It would be soluble in the chlorides, but it would 
be no longer calomel, and you wish to have it with its own pecu- 
liar properties. 

Here is the artifice you will employ. It is an English phy- 
sician, Law, who has shown us how the effects of calomel on the 
general system may be assured. Here is his manner of proce- 
dure, and it is one very generally adopted at present. The 
doses are to be very small; for instance, it may be but one cen- 
tigram at a time in sugar of milk, to augment the size and aid 
in the division of the dose ; five centigrams is thus given in 
twenty-four hours, in five or ten doses. Under this form calomel, 
notwithstanding the insignificance of the dose, produces consid- 
erable effects, and this is why : introduced in very small doses, 
it finds in the primae vise the necessary modifying agents 
to bring about its dissolution, not chloride of sodium (it is, in fact, 
very fortunate that there is not much of this salt present, it would 
make a double chloride), but it comies in contact with mucus, 
which dissolves it. It penetrates, with the albuminoid principles, 
into the blood : then a new dose arrives, very small, like the pre- 
ceding ; it is completely dissolved, passes into the circulation, and 
goes to augment the dose already present in the blood. And so 
on, the solution being thus effected for each of the doses. 



PREVENTION OF ACCUMULATION. 385 

When calomel has thus been given, very decided results 
are obtained from small doses, so much so that from one day to 
the next, sometimes, symptoms of salivation appear, and in the 
space of two days a marked sialorrhoea occurs, and after three 
days phenomena of mercurial stomatitis may ensue. If, on the* 
contrary, the same quantity had been given at one dose, and if it 
had encountered difficulties in the way of dissolution, it would 
have induced symptoms of considerable local irritation, and, 
being taken up by the hepatic gland, it would have been rejected 
from the economy. There would have been symptoms of irri- 
tation of the secreting part of the liver, purgative or cholagogue 
effects on the intestine, but no general effects. This method has 
given very good results, and is generally employed when it is 
desired to produce antiplastic or constitutional action. 

I come, now, to another aspect of the question concerning the 
accumulation of action. We have just seen what accumulation 
of doses signifies ; we will now consider what is accumulation 
of action. 

It is observed that in administering a medicament several 
days, one after the other, giving each day the same dose, the 
phenomena due to the action of this medicament become more 
and more intense. 

This may occur even when it be known for certain that all 
given each day was absorbed the day it was ingested, produced 
its effects, and had sufficient time for elimination, when elimina- 
tion could have been made in this space of time. This phe- 
nomenon of increase in the intensity of remedial action — the 
dose remaining the same — should not be confounded with the 
pseudo-accumulation of action which results from accumulation 
of doses, and in certain cases from a change in the pharmaceutic 
preparation. For it is well that you be warned that it suffices 
often to change the pharmaceutic preparation, in order to have 
symptoms more or less grave supervene, even employing tlie 
same dose as on the preceding day. This is another point which 
experience teaches us, and on which Trousseau has insisted. 
He had remarked that when he gave strychnine or mix vomica 

25 



386 PRINCIPLES AND METHODS OF THERAPEUTICS. 

in pills, and when at certain periods he was obliged to augment 
the dose and preparation, to obtain very powerful physiological 
effects, there supervened, the following day, all of a sudden, 
symptoms, of more or less gravity, of poisoning by strychnine. 
He finished by noticing that it was not alone an accumulation of 
doses which produced this phenomenon, but that also the change 
in the pharmaceutical substance had its part. That is to say, 
that after a certain time drugs become altered in the pharmacies, 
and particularly extracts, when they have been prepared for a 
time. This is why, after having administered a dose already 
considerable, of nux vomica, another extract recently prepared, 
and consequently of great energy, being given in the same dose, 
it is possible that toxic symptoms will be produced. You see 
that this is a phenomenon which differs from accumulation of 
action. 

I give you another fact: when a substance like strychnine 
is employed in the state of syrup of the sulphate of strychnine, 
when it is given in fractional doses, and when the same dose is 
repeated every day ; here there is no possibility of accumulation 
of doses, since all is instantly absorbed, and there is not either 
any change in the substance, sulphate of strychnine being always 
the same; yet, nevertheless, this progressive increase in the 
intensity of its action is observed ! And what I here say to you 
for strychnine is true for a great number of substances. How 
can this phenomenon be explained? It would seem that the pro- 
cess is as if the intervals between the successive doses adminis- 
tered of the active substance were sufficiently short, so that a 
portion of the action of the first doses persists in the system at 
the time the following dose is administered, and so on for the fol- 
lowing doses. Suppose, in this particular »case, that the effect 
of the first dose be represented by 20, and that of this effect rep- 
resented by 20 there persists the half, that is, 10. And that the 
third day there subsists 5, the fourth of the primary effect. You 
can easily understand what will happen. 

When you give the same dose, producing an action represented 
by 20, on three successive days, if there subsists 10 of the prim- 



PREVENTION OF ACCUMULATION 387 

aiy effect, you will have the second clay an effect represented by 
30, and on the third by 35. All kinds of figures might be taken 
to represent this phenomenon ; those which I have chosen are 
simple, and render account of the fact. 

We will now attempt to explain the mechanism through 
which is brought about this persistence of action of a substance, 
administered always at the same dose, but which, nevertheless, 
induces effects more and more intense, effects constituting what 
is called accumulation of action. It is to be noted that these 
phenomena of accumulation are observed, generally, with pretty 
large doses, or else moderate doses when given at short inter- 
vals, and with substances which pass slowly through the organ- 
ism. You can readily understand that there will be no accumu- 
lation with feeble doses, for they are destroyed and eliminated 
with facility, nor with substances which pass easily through the 
economy, and which act, for instance, solely on the globules. 
You know that these substances are generally eliminated with 
great rapidity, as are the gases themselves ; ether, chloroform, 
ammonia, in fine, all the substances which act principally on 
the blood, are eliminated with celerity, and accumulation is 
difficult. On the contrary, the substances which sojourn more 
or less in the system, which penetrate into the parenchyma, 
which at last are incorporated with the immediate principles, or 
with the cellular parietes; or, again, which take part in tissue 
formation, such substances are the ones which show themselves 
particularly favorable for the production of what is called accu- 
mulation of action. 

Where do you find the substances, in relation to which 
this accumulation has been cited? I have spoken to you 
of strychnine, which acts on the elements of the medulla, 
penetrating and sojourning in them. You will find the same 
true for digitalis, and it is one of the best examples. We will 
return to this latter drug, for it presents a peculiarity not 
observed for other substances. You will observe the same phe- 
nomenon with arsenic, mercury, phosphorus, and load. Lead 
furnishes perhaps the most favorable example to demonstrate 



388 PRINCIPLES AND METHODS OF THERAPEUTICS. 

what influence the mode of penetration of a substance into 
the system has on the accumulation of action, Thus, very small 
closes of lead, but repeated every day, finish, in the end, by deter- 
mining very grave symptoms, since different forms of paralysis, 
and death even, may result. These are the substances, and they 
are precisely those which adhere most, as it were, to the organism. 
Now, how should their effects be understood ? In what manner 
do they proceed in order to augment progressively, the doses re- 
maining the same, the intensity of their effects? It may be sup- 
posed that what occurs in the living organism, through the 
influence of modifying agents which we introduce for a remedial 
purpose, bears some resemblance to what occurs in a storm. 
You have seen great poplars, bent under the force of the wind, 
return toward the erect position, and again incline under the 
force of the blast to an angle of 45°, and even less, with the 
horizon. With each blast the tree is bent lower than before, and 
in greater proportion. It may be supposed that something anal- 
ogous takes place when medicaments commence to produce their 
effects ; first, a deviation in the function of the cell takes place, 
there is increase or lowering in functional activity, then a new 
dose arriving, increases this deviation. This manner of regard- 
ing the subject is admissible, but is somewhat too hypothetical, 
and does not repose on facts proven with sufficient certainty. 

Another supposition, which it appears more easy to admit, is, 
that a certain fraction of the active substance remains permanent 
in the interior of the tissue it modifies. You can well under- 
stand, to take up again our example, that if out of twenty parts 
of the active substance (say digitalis or digitaline) but ten parts 
are eliminated or destroyed each day, if ten parts remain in 
the histological elements of the bulb, at the point of origin of 
the sensory nerves, when the next day twenty new parts of 
digitaline are added, there will be thirty parts situated in the 
bulb, to modify the functional activity of the heart. It would 
seem that, in reality, it is thus events occur. So that there 
would be no great difference, in taking this view of the subject, 
between accumulation of doses and accumulation of action ; and 



PREVENTION OF ACCUMULATION. 389 

it might be said, the accumulation of doses is the accumulation 
of medicaments in the primae vise ; accumulation of action is the 
accumulation of medicaments in the organs where they accom- 
plish their destiny. And thus all is explained by this sojourn, 
more or less prolonged, in the organ which the active substance 
chooses, in its organ of election. 

This explanation is sufficient in the great proportion of cases, 
but it is insufficient as regards digitalis. For this remedy exhibits 
a very curious peculiarity, well known for a long period, but 
which has not yet been sufficiently studied in all its details, and 
to which recent works have again called the attention of practi- 
tioners. I would speak of the augmentation of the phenomena 
of digitalism, observed when its administration has been arrested. 
Thus this is frequently observed when the alcoholic tincture is 
given in the dose of twenty or thirty drops a day, or the infusion 
in the dose of fifty centigrams, or the powder of the leaves of 
digitalis. Some remarkable phenomena are thus obtained and 
have provoked much discussion at various times, but which are 
well explained to-day ; the progressive slowing up of the beating 
of the heart and the augmentation in strength of the cardiac pro- 
pulsion. After five or six days the pulse will fall to 80, from 
130 or 150, which it was at first. At this moment the prudent 
practitioner arrests the use of the drug, and leaves the digitalis 
to accomplish what remains — that is, to reduce the pulse to 60 
beats. And it happens in a great number of cases that the 
slowing up of the pulse continues, not only for twenty-four 
hours, but also for the four or five days succeeding. So that the 
pulse, which he left at 80 when ceasing to employ the remedy, 
finishes by falling to 40 beats. And this slowing up may last 
for a longer period, even, than that I have mentioned. In sev- 
eral observations a much longer delay has been cited, and my 
friend, M. Quevenne, has shown in his experiments that 
this peculiar retardation which 'follows the administration of 
digitalis might last ten or even fifteen days. Even this term 
may be exceeded. I had lately in my service at Beaujon 
a man affected with an organic disease of the heart, and to whom 



390 PRINCIPLES AND METHODS OF THERAPEUTICS. 

digitalis had been given in proper doses to render the beating of 
the heart slower. This progressive retardation lasted twelve 
or fifteen days at 54 to 45 pulsations. He left the hospital to 
see a public celebration, saying that he would probably never 
see another fete. Durozier, has cited a case where this slowing 
up lasted twenty-five days. 

I may say that for these facts the explanation given just 
now is insufficient. We contented ourselves with saying that 
a small quantity of the medicament remained in its organ of elec- 
tion, in the medulla oblongata, or in the brain, if you wish, and that 
this portion which thus remains receives each day additions from 
the new doses introduced. But in this case the medicament has 
been suppressed; another explanation must hence be sought. 
It is probably the following : a substance does not immediately 
penetrate into the organs it modifies ; during a certain period it 
is in the circulation, or is in reserve in the interstices of the cel- 
lular tissue, or in the initial lacunae of the lymphatic network 
of the organs where it is undergoing elimination, but w T hence it 
is eliminated somewhat slowly. 

It must be admitted that there is evidently an accumulation 
of doses in the circulatory system, and in all the organs, which 
may serve as a reserve for the active substance. You see that 
the more we study the phenomenon, the more certain we become 
that accumulation of action and accumulation of doses have a very 
close relation to each other. In short, it may be said : accumu- 
lation of doses is the storing-up in the prima? vise ; accumulation 
of action is the storing-up in the organ on which the remedial 
agent exercises its action. 

Now, what are the circumstances modifying this accumulation 
of action ? One of the principal circumstances, and which I have 
already placed in relief, is the rapidity with which elimination 
is produced. When I spoke to you of arsenic, I said : It is pos- 
sible that even strong doses be eliminated, but before this occurs 
they have already produced effects which, by repetition, determine 
dangerous phenomena as regards the digestive organs, and which 
may finish by destroying the sources of life. This same elimina- 



PREVENTION OF ACCUMULATION. 391 

tion, slow or more rapid, intervenes again in this instance, since 
digitalis cannot maintain its effects, unless it is held in reserve 
in the tissues. It is not then eliminated gradually and completely, 
during the period it penetrates. In effect, it is one of the sub- 
stances most difficult of elimination. It would seem to be elimi^ 
nated but by few organs, and I have reason to think that it is 
discharged particularly by the liver. What is well known is 
that it does not seem to be eliminated by the kidneys (which is, 
nevertheless, the ordinary route for most substances), and this is 
so true that the taste of digitalis has never been found in the 
urine. 

Thus M. Quevenne, who carried scientific devotion to the 
most extreme limits, said that, notwithstanding the large doses 
he employed in his experiments, he had never been able to find 
in the urine a bitterness recalling that of digitalis. You know 
that it is of such bitterness, that the smallest quantity present in a 
liquid suffices to give it a flavor which will leave no doubt of its 
presence. This is so true that when you take an infinitesimal quan- 
tity of amorphous powder of digitalis, like that of Homolle, and 
place it on the end of the tongue, it will give you a taste of ter- 
rible bitterness. And, nevertheless, it is almost insoluble in 
water. You can then understand that if, being insoluble, it 
gives so bitter a flavor, its power to indicate its presence 
must be excessive. It is to this prolonged sojourn that 
digitalis owes its power of influencing the organs apt to be influ- 
enced by it, even when its administration has been stopped. 
There is always possibility of accumulation of action for a certain 
number of bodies, for quinine in particular. It suffices that the 
doses be administered at somewhat short intervals, in order that 
a sufficiently considerable quantity of the active principle be 
always present in the economy, to end by saturating, as it were, 
the system, and thus producing phenomena of accumulation. 
This is what takes place for quinine, for morphine and for 
atropine. 

I will speak to you of other circumstances which modify 
the intensity of phenomena due to accumulation of action. 



392 PRINCIPLES AND METHODS OF THERAPEUTICS. 

This accumulation is limited by the destruction of the substance, 
and by the greater or less rapidity with which denutrition and 
disassimilation are effected. This is so true, that with substances 
essentially cumulative, as English physicians express it, especially 
metallic substances, something may be doue in opposition to this 
accumulation in the nervous system by administering iodide of 
potassium. 

Melsens, who first demonstrated this influence of iodide of 
potassium received the "grand prize" for new observations re- 
garding this subject. It suffice^, he affirms, that while individ- 
uals are exposed to emanations from lead, iodide of potassium be 
concurrently administered, to prevent there being at any time 
sufficient saturation of the nervous centres by lead for these 
individuals to present phenomena of paralysis. This is a great 
service rendered to humanity, and the prize was justly decreed. 

There is another circumstance which also limits accumulation 
of action, that is, the force of habit. Without doubt, we observe 
substances accumulate in the nervous system, and these determine 
effects more and more considerable, finally becoming dangerous; 
but there is also in our economy a disposition which may be 
expressed by the term "force of habit/' by virtue of which we 
resist more and more the action of remedial or toxic agents, just 
as we resist in like manner many exterior conditions which might 
injure us. 

We will attempt to understand in what this force of habit con- 
sists, and how it may be interpreted. It may be expressed in 
this proposition : progressive diminution in the action of modi- 
fying substances with which we are in contact. This progressive 
diminution may be due, either to the lessening of our suscepti- 
bility as regards the drug, or that we react with ever increasing 
vigor against the action of the substance. This gradual enfeeble- 
ment of the action exercised by modifying agents on our economy 
is not in equal proportion for all. There have been such differ- 
ences noted that observers have found themselves obliged to seek 
some explanation for them. 

My colleague, Bouchardat, has affirmed that these differences 



PREVENTION OF ACCUMULATION. 393 

are due to the following facts : we find on the one hand sub- 
stances which in sufficiently large doses are poisonous for higher 
organisms only; on the other hand, substances poisonous for all 
living organisms no matter at what degree of the scale they may 
be placed. Now, he affirms, poisons which are poisons for all 
forms of organic life are substances to which no one becomes 
accustomed ; on the other hand, individuals may become accus- 
tomed to substances which are poisonous only for the higher 
organisms. 

I have no wish to refute this manner of explaining away the 
difficulty ; I believe, even, that it is sufficiently accurate. But 
it leads to this conclusion : No one can become accustomed to 
poisons noxious for all living beings, because no one can become 
habituated to substances which exercise their poisonous action on 
the faculties which are possessed in common by all, such as 
nutrition and the generative functions. On the contrary, habit 
may give impunity when these substances attack faculties added 
to these and possessed alone by the superior animals, such as the 
nervous system, with its various attributes, and the faculties of an 
elevated order, which they possess, and which do not form an 
essential part of all living beings. I contend that if the propo- 
sition advanced by Bouchardat is true, it should be said that 
the substances to which habit gives no impunity are those which 
are poisonous for those functions which may be called elementary 
for all living beings ; but in such case substances which act as 
violent poisons on inferior organisms should not be tolerated by 
animals placed higher in the scale, as has been observed. You 
are all familiar with the powder of the pyrethrum roseum. This 
is a poison of extreme energy for insects, but for the superior 
animals it is almost inert ; it can hardly, even, be considered as 
disagreeable. Other plants, such as tansy, are disagreeable; they 
do not please our sense of smell, but they do not poison us. 

You see, then, that there are substances poisonous for inferior 
beings and which are without effect on superior beings, even 
when taken under analogous conditions. This peculiarity pre- 
vents me from admitting without reserve the correctness of the 



394 PRINCIPLES AND METHODS OF THERAPEUTICS. 

proposition I have just indicated. To mention it in passing, 
this possibility of substances inoffensive for the superior organism 
producing toxic effects on the inferior, gives hope that some day 
those inferior organisms which, according to Pasteur, are the 
fundamental causes of most contagious diseases, may be combated 
by means which would not be dangerous for the superior organ- 
Ism carrying in the system these contagious principles. 

I think that a distinction of more practical value might be 
made between mineral poisons on the one hand, and organic 
poisons on the other. 

Habit does not give impunity against the mineral poisons; no 
person exposed to them can escape poisoning by arsenic, or by 
lead. There are individuals who resist, more or less, but acci- 
dents are inevitably produced in the end. On the contrary, 
organic substances which are destructible are principles toward 
which we acquire impunity through force of habit. If there is 
no Mithridates for arsenic or lead, there is for opium, for bella- 
donna, and particularly for tobacco. 

Such, then, is the true distinction to be made; mineral sub- 
stances on the one hand, and organic substances on the other. 
Yet, exceptions must be noted, for there are organic substances 
against which habit gives no impunity. There are experiments 
made by Claude Bernard, which demonstrate that if a cer- 
tain dose of curare is given to an animal, it will be noticed that 
the effects last so many minutes; if the next day the experiment 
is repeated with the same dose, and the same substance, exactly 
the same results, having the same course, and lasting the same 
length of time, are obtained. It would seem that for curare 
there is no possible way of becoming habituated. 



FORCE OF HABIT. 395 



CHAPTER XXXI. 
Force of Habit. 

Force of habit ; frequent repetition ; influence of organic predisposition, or 
of local organic condition. 



Gentlemen : 

I come now to speak of the theory of " force of habit." How 
is it possible that an organism at first so impressionable tolerates 
a drug with ever increasing facility, so that in the end it appears 
insensible to doses which might bring on grave accidents ? Sev- 
eral hypotheses might be made, and it is very probable that the 
different hypotheses find application simultaneous, or by groups, 
in the various cases. 

It may be supposed that the destruction of the active sub- 
stance to which an individual becomes accustomed is effected 
with more and more - facility. It may be supposed that the 
destruction becoming more and more rapid, there never enters a 
sufficient quantity of the substance into the circulation and into 
the tissues, to produce the poisonous effects of the first doses. It 
would seem, from this hypothesis, that carnivorous animals, for 
instance, might, in the end, through force of habit, acquire the 
same immunity against substances such as the alkaloids, which 
herbivorous animals always possess. For it is remarkable that 
when the action of vegetable poisons is studied on rabbits, on 
the goat and in ruminating animals, it is seen that there is no 
great difference of action, whether the poison is introduced under 
the skin or into the circulatory system ; while in carnivora the 
action differs according to the mode of introduction. It might have 
been thought, otherwise, that it is through the rapid destruction of 
the substance in the primae viae that herbivorous animals escape 



396 PRINCIPLES AND METHODS OF THERAPEUTICS. 

the poisonous action of such vegetable poisons ; it can be easily 
understood that with greater activity of digestion the poisons 
may be more rapidly digested. Probably, also, the subjects who 
become habituated eliminate the poison with increasing rapidity. 

You all know the importance of elimination ; it is through its 
agency that we ordinarily escape the poisonous action of sub- 
stances introduced into the economy. Its activity becoming 
more and more considerable as the system reacts, it is the 
function through which the individual escapes from the conse- 
quences of the action of a poison. 

There is also another hypothesis ; it is that the energy of re- 
action becomes more and more marked. When you are exposed 
to cold, you will at first be depressed, and later become excited ; 
you thus react, and efface by this reaction the positive phenom- 
ena of the action of cold. The cold occasions at the periphery 
a diminution of temperature, corrugation of the skin, a more or 
less energetic contraction of the cutaneous dartos, and following 
these phenomena, more or less vivid redness will be observed to 
appear almost instantly, which is due to the dilatation of the 
capillaries a moment before retracted ; then calorification becomes 
exalted, and relaxation of the tissues ensues. What you here see 
produced through the action of an external agent is equally 
produced by substances introduced into the interior of the econ- 
omy. 

Thus, the susceptibility, as regards foreign substances, may 
become duller little by little, and the sensibility becoming gradu- 
ally diminished, the substance, which at first was very poisonous, 
because of the great impression it produced, slips along, as it were, 
and later passes unperceived. I repeat, these are the four hypo- 
theses that can be made ; they are all plausible, and I think that 
the whole four should be adopted to explain this immunity through 
force of habit. This presupposes on the part of the economy a 
remarkable faculty of adaptation, which might be expressed by the 
term, "organic elasticity." It is a very general phenomenon. 
You have but to examine the two kingdoms and you will see 
that it exists everywhere. It is through this elasticity that human 



FORCE OF HABIT. 397 

beings can exist over so extensive an area ; and that they can 
by either functional or structural modifications, place themselves 
in harmony with the conditions under which they are called upon 
to live. 

Man can live almost everywhere. When we go into tropical 
countries we shelter ourselves" from the excessive heat by currents 
of air; in cold countries by other artifices. We thus escape great 
extremes of temperature. I do not pretend that in every 
case we adapt ourselves to the circumstances; but you will 
observe the curious phenomena of functional modifications on 
the one hand, and nutritive modifications on the other. When 
these modifications are further accentuated, when they are, as it 
were, imprinted on a race, then you have created a new race, 
which might with propriety be called a species. 

For instance, a man from the North goes into a tropical country ; 
see how interesting are the modifications he undergoes. This 
man, of rosy complexion, becomes pale; what does that signify? 
that he loses blood globules; showing that the number needed 
for hsematosis becomes less considerable. It is one way of 
becoming adapted to a climate where there is no further need of 
so much combustion to create force, since the general temperature 
almost equals that of the body. 

Why do southern races become colored? Because of all the 
vibrations of imponderable fluids, the most active is luminous 
vibration, and to diminish this vibration it is necessary to extin- 
guish it. This is why a pigment, becoming gradually thicker, 
is produced at the surface of the skin and prevents solar radiation 
from producing the disagreeable effects it is capable of causing. 
It is the same for the modifications of the hair follicles. The 
bulb increases gradually in proportion with the needs. 

There are other forms of adaptation : Nutritive and functional 
modifications are produced ; for instance, there may be a diminu- 
tion in the activity of the respiratory apparatus and an aug- 
mentation of that of the biliary apparatus. Why? Because 
there is less to be burned, and a large quantity of nnbumed 
material to be eliminated under the influence of an alimentation 



398 PRINCIPLES AND METHODS OF THERAPEUTICS. 

which is not always in equilibrium with the needs of the 
economy. 

Consider some simple facts relating to habit: A subject has 
been confined to bed, in the horizontal position, for a number of 
days. He leaves the bed, and at the moment he rises his legs 
become violet. This signifies that there is no longer equilibrium 
between the muscular tension of the inferior limbs and the pres- 
sure the vessels are required to support. When he has passed a 
few hours in the erect position equilibrium is established. Again, 
the oftener the action of the cold shower bath is repeated, the 
quicker reaction takes place. At first precautions are necessary; 
later the subject reacts under the shower bath, the reaction being 
somewhat excessive, and finally the patient becomes entirely 
accustomed to it. 

It would seem, then, that therapeutic habit is an equilibrium 
established between the intensity of the action of a medicament 
and the reaction of the system. It is a tolerance which becomes 
established after a period of time. But this expression " tolerance" 
awakens other ideas in the minds of many physicians. It is an 
entirely different affair from that which I have just explained to 
you; especially by one school, that of Rasori. The partisans of 
Rasori give this example : When tartar emetic is given in small 
doses, it induces nausea and vomiting; and when the dose is some- 
what considerable and the subject very impressionable, there 
results emeto-cathartic effects of more intensity. Such are the 
proper effects which, according to them, belong to tartar emetic. 
If they are produced with certainty by middling doses, but are 
wanting when large doses are employed, Rasori designates this 
phenomenon by the name of tolerance. But it is to be remarked 
that even when emesis is wanting, other phenomena are produced, 
such as extreme prostration of strength, general frigidity, a cold 
and clammy sweat, a pulse either slow or very fast, depending on 
the manner of action of the medicament. Can this be called tol- 
erance? Certainly not; it is a prostration of the system! It is no 
more tolerance than the state of powerlessness into which one 
pugilist throws another when he fells him by a blow. 



FORCE OF HABIT. 399 

The proof that it is a state of prostration is, that when the sub- 
ject is attentively watched, it will be observed that at the same 
time with these phenomena I have just described there exists a 
state of stupor of the nervous system, and a general prostration 
of forces, so much so that the patient recovers with difficulty. 
There is another proof which will show you that it is not a tol- 
erance, but rather a prostration of the organism. Generally you 
will not go so far with the remedy as to produce the degree of 
stupor and of prostration which simulates tolerance, unless the 
patient first suffers from vomiting and evacuations from the 
stomach and rectum. These efforts of vomiting require consid- 
erable energy of all the muscles of respiration and all the powers 
accessory thereto; consequently, I repeat, there is loss of sub- 
stance and strength. This is why these phenomena never appear 
suddenly. It is not always in a pneumonia that tolerance can be 
immediately obtained, even in old women. I have noted this at 
the Salpetriere hospital, where from eighty centigrams to one 
gram of tartar emetic were sometimes given. 

I have seen, in such cases, pustules formed in the stomach, 
and death caused by tartar emetic. I say, that even for aged 
women, consequently, under conditions of diminution of strength, 
this tolerance was never observed to become established immedi- 
ately. When, then, does it become established ? When the 
subjects are entirely worn out, as in very grave forms of pneu- 
monia, as typhoid pneumonia. 

I have often remarked, and I make the observation almost 
daily at the hospital, that it is impossible to induce emesis in 
subjects who are in an adynamic state. Why ? Simply because 
to vomit requires considerable strength. 

What I have just said to you of tartar emetic, is observed also 
with digitalis. With feeble doses of ten centigrams, morning 
and evening, an increase of tension is determined by increase of 
the contractility of the peripheral circulatory system, and partic- 
ularly of the contractile power of the heart. If large doses are 
given, they determine widely different effects, as irregularity, 
extreme precipitation and difficulty of the circulation, increase 



400 PRINCIPLES AND METHODS OF THERAPEUTICS. 

of the oedema, even cyanosis, and finally phenomena of intense 
gravity. But this is, again, some will say, effected through tol- 
erance. ]STo; digitalis has, as it were, exceeded the strength of 
resistance and occasioned true poisoning instead of its ordinary 
effects. 

Nevertheless, there is a veritable tolerance which may become 
immediately established, and which is, as it were, a habit adopted 
without requiring time. This true tolerance merits study. Here 
is how it may be understood : it results from the more or less 
considerable resistance opposed by our organism to the action of 
modifying agents foreign to it ; and which act as medicaments. 
This tolerance is of two kinds, either passive or active. You 
will see that these distinctions are useful. 

In the first class may be considered the different phenomena 
due to the active resistance of the system. There are those 
phenomena of reaction of which I have already spoken ; reaction 
of greater or less intensity, which comes on suddenly, effacing all 
at once the immediate effects of remedial agents, or of medica- 
ments. Thus, we react against cold, or the causes of great de- 
pression; or against heat and the effects of stimulants, as by per- 
spiration, which is a means of reestablishing equilibrium between 
the internal and external heat. Then there are those phenomena 
of destruction by means of combustion ; or again, destruction by 
means of products furnished by the economy, which are a chemi- 
cal means of producing alteration of noxious substances. Finally, 
there is more or less rapid elimination, which always occurs. 

The passive means of resistance are, on one hand, non-destruc- 
tion of tlie substance, and on the other, default of absorption. 

It would seem that there are cases in which, before there has 
elapsed sufficient time for the patient to become habituated, there 
exists absolute resistance to the absorption of active substances ; 
in other cases, through the diffusion of the active substance in a 
large body the phenomena produced are very limited and may 
pass unperceived. 

If, for instance, into a large organism is introduced the same 
quantity of substance which generally produces active effects in 



FORCE OF HABIT. 401 

a small subject, it is clear that the quantity producing active 
effects in the second case may produce none at all in the first. 

What I have said here of size, may be said of various ages of 
life. We will return to this part of the subject in considering 
the various doses which shall be given at different ages, and for 
each sex. At present I wish to call your attention to the differ- 
ence between the new-born being and the adult. The same dose, 
other things being equal, introduced into the small organism, 
should there determine more considerable effects than in the 
organism twenty times larger, and in whom the quantity of blood 
destined to receive the substance is twenty times greater. 

There is also a form of tolerance which is established without 
delay through a diminution of susceptibility, through an inertia 
manifested by the system in presence of the active substance, and 
which varies with the mode of action of different substances. 
Consider, for instance, alcoholic liquids : there are nations which 
are sober, and others again which are prone to alcoholic excesses, 
by their constitutions. 

It must be admitted that the habit of sobriety or alcoholic 
excess has considerable relation with the exigencies of the climate, 
and with the impressions produced by the surroundings on the 
economy. This is so true, that the inhabitants of southern zones 
who- travel in northern climates soon acquire the habit of drink- 
ing like.northern nations. It is not through any need that they 
thus imbibe, but because of the difference in the intensity of the 
effects, which enables them to drink much. 

Thus, every traveler who has been in the northern part of 
Russia will tell you that when the cold is very intense, brandy 
can be taken like water, and without the individual being aware 
that he is drinking an alcoholic liquid. This is the true toler- 
ance ; under the influence of the anaesthetic state of the different 
surfaces with which the remedial agents come in contact, there is 
diminution of susceptibility to it. It is the same for the influ- 
ence of conditions of temperature. According to the condition 
of the individual, the rays of the sun may determine either pain- 
ful accidents, or not be felt. 



402 PRINCIPLES AND METHODS OF THERAPEUTICS. 

If a person is in good health, with no tendency to vascular 
dilatation, if there is no part of the organism in an inflammatory 
state, he may, with impunity, expose himself to the sun's rays. 
If, on the contrary, he is already subject to cephalalgia through 
congestion, he cannot do so with safety. 

There are other facts yet more singular. It would seem, at 
first thought, that every one would be equally susceptible to the 
action of a sinapism or of a blister. Yet, there are individuals 
who do not feel the action of cantharides. I have observed such 
cases. I recall to mind a poor lady affected with a stricture of 
the descending colon. I wished, one day, to produce vesication, 
but no blister would take effect. Two or three years from that 
time she proved susceptible to their action. 

It is the same with sinapisms. There are cases where the 
strongest produce no redness or pricking. This happens in 
certain conditions. Rules may be given whereby it may be 
predicted which subjects will prove impressionable, and which 
indifferent to their action. Thus, nervous, hysterical women, in 
whom there exists true analgesia, will not prove so susceptible to 
the action of a sinapism as others. Sometimes they will produce 
some redness, but no pain, which is one of the conditions of their 
revulsive action. What I have said concerning nervous wojnen 
may also be said of subjects presenting analgesia generally. 

Thus, in subjects with lead poisoning, irritating substances 
have less effect in the regions where there is analgesia than in 
other regions which possess sensibility for pain. Take opium 
and belladonna. Some patients are susceptible to the effects of 
one, others are more affected by the other. 

It may be anticipated which subjects will prove tolerant for 
opium, and which for belladonna. A subject having the pupil 
large, vascular retraction, with great tension and active contrac- 
tility of the vessels, will tolerate opium in proportion as these 
conditions are more distinctly marked. 

Inversely, if the pupils are contracted, with great vascular 
development in the brain, the subject will prove more tolerant for 
belladonna. This is so true that adults in general are little suscep- 



FORCE OF HABIT. 403 

tible to the action of opium, while they are very impressionable 
to the action of belladonna; while in children the susceptibility 
for opium is extreme, and very much lessened for belladonna. 

What is the difference? It is this: in children the cortical sub- 
stance of the brain is so vascular that it is red, and novices always 
believe in the existence of inflammation when they observe this 
state; in fact, little is necessary to cause this limit to be passed, 
and for the state of vascularity, normally very considerable but 
physiological at this age, to become exaggerated, excessive and 
morbid. Hence, children cannot tolerate the smallest dose of 
laudanum or opium. On the contrary, you may give them 
almost as much belladonna as to an adult. 

This difference for different ages is presented also between 
individuals of the same age, according to the condition they may 
happen to be in. For opium, for instance, this general rule may 
be laid down : that tolerance becomes more immediately estab- 
lished when the subject suffers from great pain, accompanied by 
the vascular retraction of which we have spoken a short time 
since. One, at least, of these conditions is necessary for tolerance 
to become established. Thus patients in tetanus take enormous 
doses of opium with impunity. It is the same for individuals 
afflicted with neuralgic pains, particularly in certain conditions. 

There are two species of neuralgia: the one due to simple modi- 
fications of nerves, the other congestive neuralgia, true neuritis, 
as Bouillaud would call it. 

One form yields to the action of sulphate of quinine and the 
other to opium. 

Certain states of obstinate insomnia are due to a state of per- 
manent ischsemia of the cerebral substance. You may in such 
cases give extremely large doses of opium without producing any 
symptom of morphinism. This is in complete opposition with 
what is observed in other cases, where the subjects are predis- 
posed to cerebral congestion, to whom you cannot administer any 
notable dose of opium without augmenting the symptoms, or 
without causing them to reappear if they were on the point of 
disappearing. 



404 PRINCIPLES AND METHODS OF THERAPEUTICS. 

There are other classes of remedies which present these same 
conditions of tolerance or intolerance, even immediately after 
being taken. Diuretics act when there exists a state of great 
tension, a condition of general ischsemia, particularly marked in 
the kidneys. 

When you give diuretics in conditions opposed to their oppor- 
tunity of action, they pass just as if they had no such action, and 
without producing their usual effects. 

Emetics present conditions of tolerance and intolerance ; when 
you give even very feeble doses of ipecac, for the purpose of 
determining, for instance, hypercrinesis of the bronchial tubes, 
you may provoke vomiting with great facility if there is already 
existing a state of irritation of the gastric mucous membrane. 

In opposite conditions, you may give not only large doses' of 
ipecacuanha, but also of tartar emetic, without any effect. For 
instance, there is nothing so difficult as to induce emesis in deli- 
rium tremens. I cannot give you the reason, but the fact is so. 
It recalls a practice common among certain physicians, and to 
which I myself have recourse occasionally, which consists in 
giving alcoholic preparations in large doses, to arrest vomiting. 

We will now consider a point which touches on the question 
of tolerance. I said to you, that through certain organic predis- 
positions there is either exaggeration or diminution of the effects 
of medicaments : and that this diminution might be carried so 
far that the medicament might appear to be completely tolerated. 
There are other circumstances, in which, under the influence of 
this same predisposition, remedial effects are -obtained opposed to 
those desired, and which are generally produced by the remedy. 

Take, for instance, opium; you know that generally it is a 
means of diminishing the secretions ; under certain circumstances 
it has an opposite action, augmenting them. 

You have, for instance, a patient suffering from the pains of 
lead colic. While these pains last, there exists profound ischseniia 
of all the abdominal organs, so marked that secretion is im- 
possible. You give opium; not only it calms the pain, but it 
produces a certain vascularity of this apparatus ; and through 



FORCE OF HABIT. 405 

this return of blood to the parts there is an increase in the 
secretion of intestinal mucus. 

Take an individual in whom diuresis is diminished or almost 
suppressed through the dimunition of the afflux of blood to the 
kidneys. You give him opium, you cause the disappearance of 
this state of ischsemia, you induce active secretion, and the kidneys 
recommence to perform their functions. This fact is exceptional, 
but is observed from time to time. 



406 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XXXII. 
Intolerance. 

Intolerance ; adjuvants ; synergetic and antagonistic substances ; counter- 
poisons and antidotes. 



Gentlemen : 

In considering the various conditions under which tolerance 
is observed, I have portrayed indirectly the history of intoler- 
ance. It suffices to reverse the picture, to take the opposite view 
of various peculiarities which I have indicated as inducing toler- 
ance, in order to have the conditions under which intolerance is 
generally observed. When we study the phenomena of intoler- 
ance, we observe that in certain conditions of the vascular and 
nervous system, any species of stimulant becomes an irritant, or 
may induce inflammation and fever. Thus, you will see patients 
suffering from a dyspeptic state, accompanied by slight inflam- 
mation of the primse via?, who cannot swallow, without suffering 
from painful irritation, even a spoonful of wine, a state of things 
absolutely preventing the use of a liquor which might aid in 
reestablishing health. 

Again, there are analogous conditions of the central nervous 
system ; there are subjects so predisposed to hyperemia of the 
brain that the smallest portion of wine is capable of exciting in- 
tense cephalalgia. You will also meet with subjects in whom the 
predisposition to vomit is so imminent, that you cannot introduce 
any substance in the smallest degree stimulating, without causing 
vomiting, alimentary substances even being rejected as though 
they were poisons. 

You will again see, in certain conditions of cutaneous irrita- 
bility, that any topical application, no matter of how mild a 
character, will excite redness, irritation, and a slight degree of 



INTOLERANCE. 407 

eczema. If the topical application is at all irritating, it will 
cause the formation of phlyctenee and bullae, and give rise to an 
inflammatory state resembling lymphangitis. 

In other subjects, where there exists an increase in the excito- 
motor activity of the medulla, nothing can be given wibhout in- 
ducing symptoms of irritation of this organ; certain subjects are 
so susceptible to the effects of belladonna, that a milligram of the 
neutral sulphate of atropine induces mydriasis and even deli- 
rium. 

I have already cited to you analogous facts as regards mor- 
phine. There are circumstances where these excessive effects can 
be explained. This is not very difficult for morphine, but more 
so for atropine. 

For morphine it may be foreseen that subjects having a 
tendency to hyperemia of the nervous centres will be liable to 
excessive effects on the nervous system; on this account the 
effects are so considerable in children. 

I have said that under certain circumstances medicines pro- 
duce effects different from those desired, and often completely 
unexpected. 

Thus, when certain agents are administered, such as digitalis, 
instead of the slowing-up of the pulse, we may have increase of 
tension and force of cardiac propulsion ; in a word, instead of 
the phenomena which are usually presented in subjects, exactly 
the opposite is observed. In such cases, the more you insist on 
the use of even moderate doses of digitalis, the more marked will 
the symptoms of asystole become. What does this prove? It 
proves that at a certain moment asystole consists not only in 
ataxia, but that there is at that moment a paralysis of the dif- 
ferent nerves — numerous, as you are aware — which animate the 
central organ of circulation. If at this moment you intervene 
with digitalis, you do but augment the state of asystole. 

I have spoken to you of some cases which appear paradoxical, 
and where phenomena entirely unexpected occur. I cited to you 
opium, which is an agent capable of inducing hypercrinesis, and 
which, in certain cases, is a means of augmenting the intestinal 



408 PRINCIPLES AND METHODS OF THERAPEUTICS. 

secretions; for instance, in dry colic ; where it calms the pain and 
also favors the return of the intestinal secretions, and even of 
the secretions of the glands annexed to the digestive tube, as the 
liver. I have explained to you the rationale of this action. 

Something just as paradoxical can be observed with purgatives. 
When you have decided that it is necessary to purge a patient, 
you may make use of drastic purgatives. But there are cases 
where the irritability is very considerable, in which you will not 
only be unable to produce the desired purgative effects, but you 
will augment the constipation. If, on the other hand, you pre- 
scribe very mild purgatives, such as castor oil, the saline purga- 
tives, such as solutions of sulphate of soda, and the bitter mineral 
waters, then you will obtain satisfactory results. What has hap- 
pened? In these cases there existed so much irritability, that, 
under the influence of the drastics, you have provoked true phlo- 
gosis and not a slight irritation; and, as you know, always when 
an inflammation is intense, not only is there not increase of secre- 
tion, but it dries up. You have but to observe patients who con- 
tract a severe cold; they commence by suffering from great heat 
about the chest, with absolute lack of secretion. The day when 
secretion takes place, when there is bronchial catarrh, that day 
inflammation is already diminished. These phenomena serve to 
explain to you in what manner the drastics act. 

From the array of facts which I have passed in review in 
these two lectures, the following rule may be drawn : The effects 
of remedial agents are more intense when the economy is already 
turned in the direction towards which the medieaments tend to im- 
pel it; the effects, on the contrary, are less intense, or what amounts 
to the same, tolerance is greatest, when the economy is turned in the 
direction opposed to that toward which the remedial agent has a 
tendency to impel it. 

Thus, if you have a subject in a state of ischaemia, and if you 
introduce substances capable of inducing hyperemia, he will resist 
the action of the medicaments. If, on the contrary, he was already 
in a condition resembling that in which the remedial agent would 



INTOLERANCE. 409 

place him, then the action of the medicament is intense, and toxic 
phenomena are induced with extreme facility. 

These deviations, these organic predispositions, have diverse ori- 
gins. A subject may be in a state of ischsemia or of anaemia; or 
in a condition favorable to phlogosis, and to hyperemia, through 
natural predisposition, as in subjects who have an inherited con- 
gestive tendency; or the individual may have acquired these 
deviations from the natural state in virtue of entirely artificial 
conditions, and it may be that remedial agents, poisonous sub- 
stances, or the conditions under which he has lived, have induced 
them. 

Here, then, we find ourselves in the presence of what is termed 
the synergia of substances, or on the contrary, their antagonism. 
That is, we have to deal with circumstances in which there ex- 
ists, as it were, an artificial malady produced by a remedial agent 
given previously, and which aids in the action, or on the con- 
trary opposes the effects produced by another remedial substance. 

I will give you a succinct history of antagonism, because it is 
indispensable to the art of prescribing, and to the comprehension 
of the phenomena induced when you administer antidotes ; or 
again, when you make use in the same prescription of substances 
antagonistic in action. 

I will first speak of the mode of action of adjuvant substances, 
or of the substances which have an action synergetic with that 
of the principal agents that you have decided to employ. There 
are here very diverse modes of action, some of which you already 
know, because they are constantly observed when the history of 
medicaments is studied. There are accessory or secondary sub- 
stances which act the part of chemical adjuvants. These sub- 
stances serve, for instance, to aid in the solution, transformation, 
and chemical metamorphosis of the substance destined to be ab- 
sorbed, and consequently favor its absorption. Thus, acids serve 
to favor the solution of bases, and reciprocally the bases that of 
the acids. 

In the second place, there is on the part of accessory sub- 
stances, which act as adjuvants, the power of preventing the 



410 PRINCIPLES AND METHODS OF THERAPEUTICS. 

topical action from passing a certain limit, and consequently they 
aid to prevent diffusion of the substances. You know, when 
the topical action is very irritating, absorption is not well per- 
formed. Consequently, we must in some cases reduce the in- 
tensity of the topical effects in order to favor absorption. 

To accomplish this, various expedients are employed as 
mechanical means, as when the substance is enveloped in gum, 
which prevents the active substance from coming in contact, in 
too large quantity at a time, with the gastric mucus. In other 
cases the adjuvant, or the corrective, constitutes with the substance 
a combination which renders it less irritating. Thus, aloes and 
scammony entering into combination with medicinal soap, divide 
the base with this kind of acid, and there results a substance of 
which the affinities are partly satisfied, and which is less irritating 
for the mucous membrane on which it is applied. 

There are other substances intended to diminish pain, topical 
irritation, and the action of vomiting, which occurs very often on 
the introduction of medicaments. These are correctives par 
excellence, and such substances are very numerous. You employ, 
sometimes, capsules containing ether, which you administer just 
before a medicament capable of producing a pain in the stomach; 
or oftener you give a few drops of laudanum ; on other occasions 
a compound pill, in which you will add narcotic substances, 
whose effects will increase those of the principal remedy. You 
will also give waters charged with gases, or the mineral waters 
which contain gases in solution, which are of a nature to prevent 
vomiting in persons disposed to it. 

There are other correctives very frequently employed, which 
are found in all ancient prescriptions, and which are, perhaps, 
somewhat too much neglected to-day. 

Empiricism has demonstrated that aromatic substances are emi- 
nently calculated to aid in the passage of a great number of active 
substances ; that the taste of the tinctures of cinnamon, of ginger 
and of cardamon, is excellent for this purpose. When you give, 
for instance, preparation of colchicum, if you desire these prepa- 
rations to be absorbed, associate them always with some one of 



INTOLEKANCE. 411 

the aromatics I have mentioned, and which prevent the colchi- 
cum from producing local effects on the stomach, and through 
that nausea and vomiting, and also prevent the topical effects on 
the digestive tube which are often the cause of diarrhoea. 

There are substauces which augment the action of the principal 
remedy, by opening, as it were, the passages of elimination. Thus, 
if you wish to induce transpiration by the aid of aromatic sub- 
stances combined with acetate of ammonia, it is well to associate 
opium with them; in certain cases it is of benefit to associate 
ipecacuanha with them. Why? You will say that opium is 
diaphoretic of itself, and passes in part by the skin, that it even 
determines eruptions ; but it is not a very powerful diaphoretic ; 
the preparations of ammonia are certainly more energetic, in this 
respect, than opium. Yet, when you wish to have as abundant 
transpiration as possible, through the old means of the materia 
medica, it will be of benefit to combine the action of the diapho- 
retics with that of opium, or of ipecacuanha, for opium has a 
tendency to relax the vessels of the skin, lights up the face, and 
tends to render more active the cutaneous secretions. 

Ipecacuanha has a somewhat analogous effect, but accomplishes 
it by a widely different mechanism. Employed in small doses, 
as in Dover's powder, by the state of nausea into which it throws 
the patient, it causes a tendency to perspiration. Every one has 
remarked that those who suffer from nausea have such abundant 
transpiration that the sweat stands in beads on the face. 

Digitalis produces entirely contrary effects, through the tension 
it produces and the more energetic cardiac action. It has a 
tendency to induce diuresis, and it does this by itself and with- 
out the aid of any other substance. But, if you wish to have 
passed by the kidneys a large quantity of a remedy intended to 
modify the mucous lining of the bladder, you may add digitalis 
to the mixture, and you will obtain more considerable diuresis ; 
while if you add opium there will be greater tendency to pass by 
the skin. 

There is another modification of this directing action pre- 
sented by some substances. 



412 PKINCIPLES AND METHODS OF THEKAPEUTICS. 

I have already spoken of what I term directive bodies, 
which sometimes seem to give their veto to the passage of a sub- 
stance, and in other cases cause it to pass by a route which it 
never follows of itself. I instanced that camphor prevents can- 
tharides from passing by the kidneys. I cited to you also iodine, 
which, combined with iron, compels the iron to pass by the sali- 
vary glands, although it never follows this route except under 
these particular conditions. You do not observe this with the 
sulphate or carbonate of iron. Another condition in which 
secondary, or accessory substances may add something to the 
effects of the principal substance, is when these ingredients, 
although having less effect than the principal substance, act 
exactly in the same manner, and are true synergies, adding to the 
effect of the principal substance. 

The bitter tonics afford an example. It is remarkable to 
observe that bitters, no matter what their origin, exercise always 
the same action, the only difference being in the intensity. Thus, 
when you use a concentrated solution of bitter principles, as for 
instance of quassia amara, and introduce it under the skin of a 
frog, you will bring on tetanus, exactly as with strychnine. 

Analogous facts are observed with the other bitter principles, 
so that it would seem that there is simply a decreasing curve from 
the highest, that is strychnine, down to the light bitters furnished 
by indigenous plants. It is clear that if you associate these dif- 
ferent substances, the various effects are combined, and an active 
compound is obtained. 

Emetics may be divided into two categories : those which cause 
vomiting by acting on the periphery, and those which, on the 
contrary, act on the bulb ; those which act in the manner of gas- 
tritis and those which act in the manner of meningitis. 

These emetics can be associated. A common prescription is 
one gram and a half of ipecacuanha with fifty centigrams of tar- 
tar emetic. This association is a good one, and induces vomiting 
with more certainty than either separately. In the same way 
might be associated the various emetics which act on the bulb. 
The exosmotic purgatives aid each other mutually, as you are 



SYNERGIC ACTION. 413 

aware ; they are almost always associated either in the prescrip- 
tions which we order, or naturally in the bitter mineral waters, 
which have nearly all the same composition, and spring, for that 
matter, from the same kind of strata. 

Another occasion where an auxiliary effect is obtained is when 
we associate narcotics which do not act in an identical manner, 
but have at least analogous action. One kind affects one portion 
of the nervous system, the others another division. 

Take, for instance, a prescription which contains belladonna, 
opium, ether, and cherry-laurel water ; these substances, which, 
when alone, affect distinct divisions of the nervous system, when 
associated, act together and produce similar general effects. 

Opium acts with preference on the cerebral hemispheres ; bel- 
ladonna produces more notable effects on the organ of vision and 
predisposes also to slumber; ether is a means of diminishing 
general sensibility ; cherry-laurel water exercises its influence on 
hsematosis. But by this combination a subject is rendered calm 
with much more facility than if any one of them was used alone. 
This is a case where substances differing from each other in 
effects act in unison when combined. 

You will find the same to be true of what are called complete 
purgatives. There are purgatives which act on the contractility 
of the intestine ; there are others which act by irritating the mu- 
cous membrane, and which augment its secretion ; others which 
act by irritating the liver, and consequently produce hepatic 
secretion. You may combine all these with substances which are 
particularly exosmotics. If you associate these agents, you have 
a complete purgative, like the black draught of the codex (French), 
which often acts much better than a simple purgative. 

By this association of three species of purgatives, results of 
more certainty are obtained with more facility and less cost than 
with a drastic of great energy but acting in one way only. 

There are, finally, cases in which substances which are associated 
each affect one organ only, or one emunctory, and each acts inde- 
pendently ; but from the united action of all there results increased 
therapeutic effects than from any one alone. 



414 PRINCIPLES AND METHODS OF THERAPEUTICS. 

Take, for instance, a case of cachexia with dropsy; we give 
tonics to reestablish the forces and render the patient more sus- 
ceptible to the action of remedies ; then may be given purgatives 
and diuretics, which produce the evacuation of the water held in 
the cellular tissue and the serous cavities. 

Take, again, the dartrous diathesis; we give, it may be, arsenic, 
but at the same time we employ various means to act on the skin 
and on the digestive tube, in order to produce more or less intense 
revulsion toward these organs. 

Take, again, a syphilitic patient; at the same time that we give 
a substance capable of causing the disappearance of the disease, 
we give, also, tonics, to prevent the patient from losing in gen- 
eral health through the influence of the virus. 

In meningitis we give bromide of potassium and calomel, which 
is an agent of antiplastic action ; but at the same time we produce 
revulsion by irritating applications to the extremities, where we 
place either sinapisms or blisters. All these means concur to the 
same end. These substances are not really synergic; they do not 
become so unless we take the organism to be a living unity; it is 
through the solidarity of the various organs that we obtain revul- 
sive effects, because the sympathy which exists between the various 
organs is the cause that the action exercised on one is felt in the 
others ; and as it would seem that at any given moment we have 
but a certain quantity of force, when revulsion or derivation or 
marked secretory irritation is induced, the whole system is affected, 
and any morbid process going on in another part is checked, 
because it has not the necessary materials for its development; 
this is one manner of explaining the effects of revulsion. 

In another class of cases there are remedial substances which 
oppose obstacles to the action of the principal agent. These are 
said to be antagonists; they may be distinguished into chemical 
and pharmaco-dynamic antagonists. 

The chemical antagonists were alone known to those who have 
preceded us. They embrace those substances known to-day as 
counter-poisons. The recent acquisitions of science have shown us 
also antagonistic effects through pharmaco-dynamic action. 



ANTAGONISM. 415 

From this what is called therapeutic antagonism had its origin. 
T have proposed to term it antidotism, because the other term 
already exists in pathology. There are, then, chemical antagonists 
and pharmaco-dynamic antagonists. 

The number of cases where chemical antagonists show their 
power is considerable. For instance, we introduce into the stomach 
a substance destined to act by its alkaline qualities; it comes in 
contact with chlorhydric acid and becomes a salt. In other cases 
we give phosphoric acid; it comes in contact in the stomach with 
alkaline substances, combines with them, and then the urine 
hardly reveals its presence. 

• In other cases, soluble salts are introduced into the primae vise, 
where they meet with chloride of sodium, and form insoluble 



In the same way tartar emetic may be destroyed, as also the 
alkaloids. Thus, there are quite a number of circumstances by 
which the action of medicaments is prevented. 

But dynamic antagonism, or real antidotism is much more in- 
teresting. Without any doubt the antagonistic value of varieties 
of substances has been much exaggerated. Therapeutic antagon- 
ism is frequent, but has not the value usually accorded to it. It 
may be said that there exists hardly one case in which two sub- 
stances having different actions may become directly opposed one 
to the other, so as to neutralize each other regularly and defi- 
nitely. 

There is, perhaps, one exception; the case of eserine and 
atropia. It was known from the time Calabar bean was intro- 
duced, that it was a myotic agent, and it must have been imme- 
diately understood that it was the opposite of belladonna. Re- 
searches were made regarding the conditions under which this 
antagonism was produced, by Bourneville, in France, and by 
Fraser, in England. What happens is this : atropine, as you 
know, diminishes the activity of the pneumogastric ; eserine, on 
the contrary, augments its power. In other words, eserine di- 
minishes the number of cardiac pulsations, while atropine singu- 
larly augments them. Eserine augments tension, atropine di- 






416 PRINCIPLES AND METHODS OF THERAPEUTICS. 

minishes it. These are, for that matter, correlative facts. Accord- 
ing to Marcy, tension is diminished when the number of pulsations 
is augmented. Eserine augments the secretion of the salivary 
glands, as also of the lachrymal, intestinal and renal glands. 
Atropine diminishes all the secretions. Atropine diminishes the 
contractility of arteries; eserine that of the veins. Atropine 
produces mydriasis and eserine myosis. It may be said that 
opposition exists at every point between the two. 

Notwithstanding this, there are circumstances which demon 7 
strate that, this antagonism is not so absolute as might be believed. 
If eserine often diminishes the contractility of the veins, in a 
certain number of cases it augments it when given in small 
doses. If the myosis determined by eserine is placed in com- 
parison with the mydriasis determined by atropine, there is no 
equilibrium between the two. The myosis is feebler than the 
mydriasis, and this last is of longer duration. Consequently, 
you can conclude that the two substances cannot serve recipro- 
cally as antidotes. What then is not obtained in this perfect 
case, you most certainly will not have in other cases, when, for 
instance, belladonna is compared with opium. 



ANTAGONISM BETWEEN MOKPH1NE AND ATEOPINE. 417 



CHAPTER XXXIII. 
Antagonism between Morphine and Atropine. 

Therapeutic antagonism in general. 



Gentlemen: 

Much has been said concerning the antagonism between mor- 
phine and atropine. 

Von Graefe was the first to administer belladonna in cere- 
bral affections presenting myosis, under the impression that since 
belladonna determines mydriasis, when there exists spontaneously 
a morbid state accompanied by contraction of the pupil bella- 
donna should give good effects ; and inversely, he gives opium 
when there existed dilatation of the pupil. He thus obtained 
therapeutic results of great value. I have followed this example, 
and in many cases I have had reason to be well satisfied with 
the results. Recently, I had, at the Beaujon Hospital, a woman 
brought in in a state of delirium ; five centigrams of morphine 
had been injected hypodermically, and internally she had taken 
five grams of chloral and I do not know how much bromide of 
potassium. 

When I arrived to make the morning visit she was in a state 
of violent agitation ; her eyes wild and injected, the pupils con- 
tracted. I considered that in such a case opium would not be 
of benefit ; that a substance capable of dilating the pupil would 
be more appropriate than atropia. But as I was experimenting 
with duboisia at the time, which is an alkaloid which resembles 
atropia and which presents immense activity of action, I injected 
a milligram of it hypodermically. In the space of ten minutes 
calm was restored, the agitation and vociferation of the patient 



418 PRINCIPLES AND METHODS OF THERAPEUTICS. 

ceased, and when we returned to her a short time afterward the 
pupils were dilated, her eyes less injected, and when it was ne- 
cessary, shortly after, to remove her, it was with great difficulty 
she was awakened. You can see that this was a real triumph. 
One must thus be governed by the anatomical conditions in which 
the central organ of the nervous system is found. 

I repeat, this antagonism is of benefit to us ; it shows us the 
conditions under which certain means should be employed, and 
it teaches us under what conditions we may oppose mor- 
phine with atropia, and the reverse. 

But there should be no illusion on the subject; this antagonism 
is but partial. My regretted friend, Behier, who took up every- 
thing with passionate energy, had been struck by this partial 
antagonism, and went so far as to think, with many others, that 
this opposition was absolute ; that it occurred in every case, and 
that, consequently, these two substances were veritable antagon- 
ists, and that from the moment the knowledge of this fact was 
known to science there was no further occasion for anxiety in poi- 
soning by opium or morphine, since there existed a means of intro- 
ducing these substances into the cellular tissue, and thus their 
effects can be always assured. This view is erroneous. It has 
been seen that this antagonism is not sustained when large doses 
are employed ; toxic phenomena appear in such cases, even when 
the two drugs are simultaneously given; the symptoms of stupor 
appear to be more generalized, but they are not in the least 
diminished by the particular effects of either of the substances. 

You will find in an excellent work — a book I cannot recommend 
too much to you, that of John Harley — excellent accounts of 
opium and belladonna. He demonstrates by a series of varied 
experiments, very well made, that not only there is no antagonism 
for elevated doses, but that even there is increase of effects; and 
so when considerable doses of atropia are employed to combat 
toxic morphinism, more rapid toxic effects and death with more 
certaintv are produced. 

You may ask how does it happen that the illusion has per- 
sisted so many years; and why the journals report cases in which 



ANTAGONISM BETWEEN MORPHINE AND ATROPINE. 419 

poisoning by laudanum has been efficaciously combated by atropia, 
or belladonna? 

It is always the same story ! Illusions prevail, because the natu- 
ral course of diseases is ignored. Every observer has believed 
that excessively large doses of laudanum or of atropia are neces- 
sarily and fatally mortal ! This has been believed so firmly, that 
the antagonism has been considered perfect, simply because the 
patients recover. A man is in a state of coma from opium ; hypo- 
dermic injections of atropia are made; he recovers; is it a success 
for atropia? not at all. 

One day, a druggist in the vicinity of the hospital St. Antoine 
brought us a woman who had just bought laudanum from him 
and had swallowed it in his presence. There had been sufficient 
laudanum taken to poison many persons. The terrified druggist 
carried the woman to the hospital ; there they prepared to admin- 
ister belladonna in large doses. The woman remained a time 
intoxicated ; she then fell into a state of profound stupor, from 
which she did not revive for a long time. The interne, who had 
administered belladonna, was enchanted; he had recalled the 
poor woman to life. Unfortunately, this woman confessed that 
she was in the habit of taking laudanum, and that the dose was 
a trifle larger than she ordinarily took. In order to procure it, 
she caused prescriptions to be written, and thus she got large 
quantities of laudanum, which she drank, and which produced a 
sort of intoxication, followed by a slumber with dreams worthy 
of being sung by the Spanish poets. This woman was received 
later, at the Neckar Hospital, where she repeated what she had 
before said, that she drank laudanum as other people drink 
wine. 

There is a case of poisoning by atropine, where there was no 
intervention, and which will show you that poisoning, even of 
the most violent kind, is often followed by recovery. One of 
my former patients, an advocate, was subject to violent attacks 
of cephalalgia. This, but a slight malady for individuals with 
much leisure, is of gravity for persons who are obliged to 
work on fixed days. He often asked me to rid him of this 



420 PRINCIPLES AND METHODS OF THERAPEUTICS. 

headache. I prescribed a well regulated manner of living, with 
a little bromide of potash. One day, at a friend's house, he met 
a physician who said to him : " What ! Professor Gubler cannot 
rid you of your headache ! it can be done with ease ! " The ad- 
vocate did not wish to receive advice in a reception room; but 
one day, when I was in the country, he had an attack of head- 
ache, and as I could not come, he went to see his physician. 
He wrote his prescription, ordering ten centigrams of sulphate of 
atropine in thirty grams of water. He told him to take the 
mixture in doses of a teaspoonful until the headache had disap- 
peared. My patient thought that a teaspoonful was very little, 
he took a dessertspoonful, that is, something like six or eight 
grams, of a solution containing ten centigrams in thirty grams. 
Hardly had he swallowed the liquid when he felt a strange sen- 
sation of malaise, and was seized with sudden delirium. He rose 
from the chair, entangled his foot in his paper basket, thinking 
he was in his bed, and fell. He remained thus until the next 
morning, no one having heard him fall ; then, in the morning, 
feeling cold, he became conscious, but could not distinguish any- 
thing clearly. He recovered completely ; I saw him the next 
evening ; the pupils were even then much dilated, but there were 
no longer any signs of intoxication. Remember, that nothing 
was done to aid in his recovery. Are you acquainted with many 
cases of poisoning by atropine with so strong a dose ? Three 
centigrams swallowed at once and in solution ! When one has 
witnessed facts of this kind, he is not very apt to believe much 
in the story of the antidotism of atropia and morphine. 

I would advise you not to place implicit confidence in such 
antidotism, and not to imagine that it is enough to give as large 
doses of atropine as has been taken of laudanum, in order to 
resuscitate the patient. 

You see, then, here are two substances concerning which the 
doctrine of antagonism pushed sometimes as far as antidotism 
has been established. 

These two substances are not true antidotes. In fact, in order 
that the antagonism should be complete, the reunion of a num- 



ANTAGONISM BETWEEN MORPHINE AND ATROPINE. 421 

ber of conditions, such as are almost never met with, is necessary. 
It would be necessary that they should enter into antagonism in 
all the organs on which the action of either one of the sub- 
stances is affected. For if there is one point alone which escapes 
the action of the counter-poison, then you will, it is true, have 
determined contrary phenomena in certain favored organs ; but 
you will also have permitted the progressive, excessive and fatal 
development of all the accidents in another organ. 

I will take an example : You are acquainted with the effects 
of chloroform when administered by the respiratory passages. 
It first produces phenomena of excitation, then of stupor, and 
these phenomena follow each other in the following order : 
first, the cerebral hemispheres are affected, then the organs of 
special sense, hearing being the last sensation lost; after the 
hemispheres, it acts on the medulla. Later, and at an advanced 
stage, it acts on the bulb, on the origin of the pneumogastrics, or 
the "vital knob," as Flourens has called it. 

Suppose that you are present at a case of poisoning by chloro- 
form and that you have at hand strychnia. The chloroform has 
thrown the subject into a state of absolute relaxation; you call 
to mind that Claude Bernard has 'said strychnia is a means of 
reviving the movement, and of exciting in the highest degree the 
excito-motor force of the medulla : here is a fine occasion to em- 
ploy the counter-poison. If you give the strychnia you will re- 
vive the voluntary muscles, you will much augment the power 
of the excito-motor action of the medulla; but you will not act 
on the bulbar centre in the medulla oblongata. But it is pre- 
cisely this centre that is affected in accidents of such gravity, 
and it is through it that death ensues. "When the organ holding 
in dependence the central organ of circulation and respiration is 
compromised, there is no time for delay. 

You s.ee, then, that it does not suffice to have a generalized 
antagonism; it is necessary that it be produced on every organ, 
and particularly in the organs essential to life. It is necessary, 
also, that the intensity of the action of the substance playing the 



4'Z'Z PRINCIPLES AND METHODS OF THERAPEUTICS. 

part of antagonist be adequate to neutralize the action of the 
noxious toxic substance. 

For, finally, supposing that you have a perfect antagonist in a 
substance like, for instance, eserine for atropia, if you give a 
feeble dose of eserine, you will not combat the effects of a very 
large dose of atropine. This example shows that if you ad- 
minister, in equivalent doses, a substance of which the action on 
the organs essential to life will not be equivalent to that of the 
poison, you have accomplished nothing. Thus, you will never 
succeed in calming poisoning by strychnia, through the aid of an 
alkaloid like solanin, which is less powerful than strychnia. 

There must be opposition in all the organs, and the action of 
the two substances be equivalent, so that the antagonist be 
adequate to neutralize the effects of the toxic substance. The 
substances which are used as antidotes for each other must act in 
an inverse manner on the organs. 

Take, for instance, tetanus; it is essentially characterized by 
tetanic rigidity, which is convulsive, and prolonged in all the 
muscles, and particularly in those which act in extension. But 
this rigidity, this state of contraction, which essentially consti- 
tutes tetanus, may be due to several conditions: it may depend 
on an increase in muscular contractility, or there may be greater 
irritability either of the motor or associated sensory nerves ; or, 
again, it may result from the excessive augmentation of the 
excito-motor action of the medulla. 

Instead of one of these conditions, there may be association 
of three or four of them. This admitted, you can understand 
why the hopes conceived regarding the good results of woorara, 
in spontaneous or artificial tetanus, have not been realized. 

Yella (of Turin), having witnessed the experiments of Claude 
Bernard on woorara, inferred that, since it had placed the con- 
tractile system in a state of complete resolution, it would have 
the power of calming the symptoms in tetanus, and of opposing 
the action of strychnia. This inference is true if one be con- 
tent with objective phenomena. That is, if you introduce woorara 
in sufficient quantity to combat the tetanic convulsions, observe, 



ANTAGONISM BETWEEN MORPHINE AND ATROPINE. 423 

these convulsions will lessen, and relaxation will ensue. Have 
you triumphed ? Do you believe that your patient will recover 
because his muscles are somewhat softened ? Not at all ; although 
you have obtained a fine result as regards the contractions, the 
patient is no better, in most cases, because woorara acts but on 
one of the conditions of tetanus, and not on all. 

What action, in fact, has woorara ? We know its action through 
the experiments of Claude Bernard, and particularly through 
those of Vulpian. Woorara acts, if not entirely on the tissues 
of muscle alone, at least on the terminal expansions or terminal 
plates of the nerves in the muscles themselves. It is not possi- 
ble to prove that the action is limited to the muscles ; but through 
experiments very well made, it may be concluded that woorara 
does not act on the medulla, on the trunks of the nerves, not 
even on their peripheral divisions; so that it must be said that it 
acts on the muscles, or at most on the expansions of the peripheral 
nerve extremities. 

If tetanus results not only from a local excitation of the mus- 
cles, which is not of great account in the production of the phe- 
nomena, not only from an excitation of the sensory nerves, which 
are the means of conduction of sensations from the periphery 
towards the central organ, but if it results also and particularly 
from the excessive increase in excito-motor activity of the me- 
dulla, you can understand that with woorara you produce no 
effect on the medulla, and consequently you accomplish but 
little. 

On this account you see so often negative and so seldom posi- 
tive results. 

In order that an antagonistic substance prove efficacious it 
must act not only on the same division of the apparatus, but also 
it must act by an opposite mechanism to that by which the toxic 
substance acts. I spoke a short time since of a theory of more 
facility of nervous discharge than under ordinary conditions, as 
explaining tetanic spasms. Such an augmentation of the excito- 
motor activity of the medulla may depend on hyperemia, with a 
state of nutrition more active than under normal conditions; also 



424 PRINCIPLES AND METHODS OF THERAPEUTICS. 

on the possession of more considerable power on the part of the 
nervous system to become charged with force. 

In such a case, if the antagonistic substance act in preventing 
hyperemia, or by diminishing the combustions favorable to the 
overcharging of the nervous system ; while, on the other hand, 
the toxic substance acts in an inverse manner, that is in augment- 
ing the capacity of the medulla for excito-motor action; under 
such conditions you will have very incomplete results. 

If, for instance, in a case where strychnia has excited the 
capacity of the medulla for action, you give ergot in order to 
diminish the quantity of blood going to the medulla, you will 
have done nothing but diminish the increase of excito-motor 
activity. You must find a substance having an action opposed 
to that of strychnia. This substance would seem to present itself 
in aconitin. This drug exercises an influence opposed to that of 
strychnia, and favors the incessant discharge from the medulla, 
just as if you gave a pointed form to the conductors of the elec- 
tric machine, which would allow the electric fluid formed on the 
plate to escape. But aconitine would not give the effects 
expected from it ; because it acts on other elements than the 
medulla, and would rather serve to add to the effects of strych- 
nia itself. 

Finally, the antagonistic action induced therapeutically should 
be of equal duration with the toxic action of the poison to which 
it is opposed. If you wish to combat the mydriasis produced 
by atropine by eserine, you will be obliged to have recourse to 
it at each instant. This is of sufficient facility when the eye is 
in question. But when one has to deal with an internal organ, 
it is more difficult ; so that, supposing you have the reunion of 
all the conditions I have laid down, if the effects do not last 
after a few moments, the unfavorable symptoms will reappear. 
When the necessity of the reunion of all these various conditions 
in order to make a good antidote is taken into consideration, it 
it easily understood that there is none perfect in existence to-day, 
and I fear there never will be. 

Nevertheless, the number of antagonistic substances is consid- 



ANTAGONISM BETWEEN MORPHINE AND ATEOPIA. 425 

erable, and under the articles devoted to remedial agents a chap- 
ter is always placed containing the antidotes and adjuvants. 
Yes ; the number of antagonists is immense ; it may be said that 
there exist antidotes for all the substances which might be men- 
tioned ; only they exercise but partially their action, or they do 
not exercise it with the intensity necessary to prove true antidotes. 

Take, for instance, opium ; it has for antidotes, coffee, sulphate 
of quinine, strychnia, bromide of potassium, digitalis, etc. Is 
there one of these efficient? No. I have just shown you that 
belladonna is not. Coffee exercises its action on the cerebral cells, 
of which it augments the activity. It is, then, efficient for that 
part ; but this does not prevent opium from continuing its effects 
on the other divisions of the nervous system, and on the sensory 
nerves. Sulphate of quinine is an antagonist of opium, without 
doubt. I showed it to be so, years ago, to a certain extent. 
While opium favors combustion and augments the volume of the 
capillaries, sulphate of quinine slightly opposes all these phe- 
nomena, but it does not prevent opium from manifesting its 
effects when it is employed in large doses. I could say as much 
for strychnia, digitalis, and bromide of potassium. 

Antidotes are not wanting for strychnia. I mention opium, 
which is, at the same time, a remedy in spontaneous as in trau- 
matic tetanus. Chloral is very good. But these are substances 
which narcotize particularly the sensory nervous system and the 
cerebral cells ; they are hypnotics. Yet this does not prevent 
strychnia from exercising its peculiar influence on the spinal 
centre in a manner to produce tetanus. 

There is, also, an antagonism existing between ergot and 
strychnia. This would be curious, and deserves to be further 
demonstrated. 



426 PRINCIPLES AND METHODS OF THERAPEUTICS. 



CHAPTER XXXIV. 
Antagonism (Continued). 

Influence of the size of the body; of sex; of age; of temperament ; of man- 
ner of living ; of race ; of climate. 



Gentlemen: 

We will turn to the antagonism between bromide and iodide 
of potassium. There exists a certain antidotism between the two 
substances. Bromide of potash produces a state of calm in all 
the organs; it is a sedative, while the other is an excitant; but 
these substances are synergic at other points of view, and they 
cannot, consequently, play the part of antagonists efficiently. 

Take the substances which augment haematosis, which increase 
respiratory combustion; alkaline substances, in small doses; opium, 
by its action on the capillaries; the neutral salts, which in the 
serum of the blood play a part on which I have insisted. Com- 
pare them with others — the free acids, the essential oil of bitter 
almonds, the substances producing cyanosis in general, and arse- 
nious acid, which has a calming action on the phenomena of hae- 
matosis; are these substances veritable antagonists? No; for you 
will often meet with certain ones among them which we use in 
opposition to each other, which, nevertheless, have effects which 
are similar. 

Consider the plastic substances as opposed to the anaplastic; 
thechalybeates, perchloride of iron, the tonics in general, quinquina 
on one hand ; on the other mercurial preparations and alkaline 
substances. These substances have a very different action on 
blood formation, but they are very far from being antagonists. 
Yet they are often combined in order to act on different regions ; 
in general w© may say there is a slight antagonism between a 



ANTAGONISM BETWEEN MORPHINE AND ATROPIA. 427 

great number of substances ; or even that it is impossible to find 
any substance which does not present antagonism on some point 
when compared with any other. But the existence of extensive 
antagonism is an exceptional fact; some substances may modify 
the effects of certain others, but oftenest this antidotal action is so 
limited that it will never do to employ them in opposition to 
each other, as a means of cure. 

When the older physicians employed antidotes, when, to-day, 
we recommend substances to combat poisoning, we have several 
ends in view, and we reach them by different means. Among 
the antidotes there are true counter-poisons capable of neutral- 
izing chemical action. We have substances which act in pro- 
voking hypercrinesis — that is, energetic excretion, and then they 
open the issues for the elimination of the poison, whatever it 
may be. 

There are other substances which exercise a stimulating action, 
and which have been considered, up to the present, simply as 
adjuvants, such as ipecacuanha. But the new experiments of 
Pasteur lead me to inquire if the stimulating action provoked in 
persons under the influence of a poison, if the stimulation 
recommended, for instance, in rattlesnake bite, has not another 
result, which is to elevate the temperature to such a point that 
it becomes impossible for the poison to germinate in the 
organism. 

What is certain is, that all the remedies employed in 
tropical countries inhabited by venomous animals to combat 
such poisoning, count always among their properties the power 
of producing an artificial febrile state. Such are alcoholic sub- 
stances, aromatics, and all those which the older physicians called 
alexipharmac agents. 

Of like significance is the name guaco, in Mexico, which is 
that of all antidotes, no matter from what plant they come and 
of what family they may be. So, also, in Brazil, in all the vast 
extent of the basin of the Amazon, all the substances to which 
is attributed the property of combating poisoning are called 
jaborandL 



428 PRINCIPLES AND METHODS OF THERAPEUTICS. 

I add, that in the substances properly called antagonists 
are found combined in the same preparation properties capable 
of inducing hypercrinesis, with others inducing febrile action 
and diffusible stimulation. 

Among the conditions which affect medicinal action is the 
size of the body. As a rule, the larger the subject, the 
more considerable the size of the body, the less marked 
will be the physiological and, consequently, the remedial effects 
of an active substance. The same dose is excessive for the 
child, moderate for the adult of ordinary stature, while for a 
giant it would be less than was needed. 

Qu6telet, who has done much toward the statistics of physiology, 
published, in 1833, a table, established by numerous experiments. 
He places on one side men, on the other women ; he takes 
them at all ages, he takes the mean of numerous weighings, and 
here are the results : — 

At birth, a male infant weighs 3 kilos., 200 grams ; a female 
infant, 2 kilograms. At one year : boy 9 kilos., 450 grams ; 
girl 8 kilos., 790 grams. At two years : boy 11 kilos., 340 
grams; girl 10 kilos., 670 grams. 

Thus the weight is seen to increase in the two sexes, but 
there arrives a time, at about the age of 12 years, when the male 
child, who up to this time had always weighed more than the 
female child, loses somewhat in proportion, and equilibrium be- 
comes established; at 12 years both weigh the same — 29 kilos., 
820 grams. At this period the weight of the young boy is slight- 
ly inferior to the half of what he will acquire when arrived at 
his maximum, which is 63 kilos., 670 grams, while the maximum 
for a woman is 56 kilos., 160 grams. 

Consequently, at twelve years of age, the young girl weighs 
more than the half of what she will finally attain. 

Weight augments up to the age of forty years for men ; up to 
fifty years for women. In man, what augments principally are 
the muscular masses ; while in women the augmentation is in 
fatty materials. 

After these two epochs (forty years for men, and fifty for 



SIZE OF DOSES. 429 

women), weight diminishes, and at ninety years is 57 kilos. 830 
grams for men, and 49 kilos. 330 grams for women. 

These statistics may be applied to posology. If the dose for 
an adult be considered as unity, the dose under twenty years and 
up to fifteen is two-thirds; the dose at fourteen years is half; 
at seven years, one-third; at four years, one quarter; at two 
years, one-eighth ; under that age, the twelfth, or the fifteenth. 

Another rule is, if you employ a dose of 20 for an adult, you 
have but to diminish the dose by one part for each year toward 
childhood ; but if you follow this rule, you will give doses which 
will prove too large. 

If we consider the results shown by clinical experience, and 
bear in mind the importance of the size of the body, we should 
say that, in general, it is the weight of the individual which 
should serve as the basis for the dose. Here is how I would 
establish the doses at different ages : I would say, taking for 
point of departure the adult, the adult dose being considered as 
unity ; at fifteen it will be two-thirds ; at twelve years one-half; 
at two years one-sixth ; at one year one-seventh ; between birth 
and the end of the first year the dose would vary according to 
the substance employed, from one-tenth to one-twentieth. Be- 
yond the age at which we place the limits of adult age, that is, 
after the forty-fifth year up to confirmed old age, the doses vary 
naturally. But here it is no longer a question of weight, as the 
weight does not change in any considerable degree; but it is ac- 
cording to the conditions of reaction presented by the economy 
that the proper dose is to be determined. 

As for women, the absolute dose for man at unity maybe 
diminished by one-eighth for them ; the dose is, for that matter, 
variable. 

Take, for instance, one gram of sulphate of quinine, the dose 
for an adult male ; if you diminish it by one-eighth, you will 
have the dose that should be given. You may diminish it one- 
sixth, if you take into account the smaller proportion of blood in 
circulation. 

For, although the determination of the amount of blood in the 



430 PRINCIPLES AND METHODS OF THERAPEUTICS. 

human subject is difficult, there is reason to think that, while in 
the male there is six kilograms of blood, in the female there is 
but five. The difference in weight is not as considerable as the 
variation shown in the supposed quantity of blood in the male 
and female. 

Here the question presents itself; should we consider the 
weight alone, or the quantity of blood? For those who admit 
that all the chemical and physiological changes take place in the 
blood, the blood would seem of main importance ; as for us, for 
I hope you have come to partake my opinion, we think that the 
blood is not the usual theatre of action of remedial agents. We 
do not attach the same importance to it in a positive point of 
view; but what we would consider of more importance is the 
bulk of the solids in which the remedial substances will be dif- 
fused. 

The larger the brain, the more morphia will be needed to in- 
duce sleep, to benumb the cells of the cortical substance. As 
much may be said for the other parenchyma? and for the other 
organs of the economy. 

The blood has also its importance, but not so much as has been 
attributed to it by a number of physicians. It contains albumen, 
and consequently it is not merely a liquid mass in which the 
active substances will be diluted. Not only is it a diluent for the 
agent, but coming in contact with the plasma it envelops it, and 
this more markedly when the active substance is in feeble dose, 
and meets with a large proportion of blood. Thus, the blood is 
an agent producing division ; it is a means of attenuating the 
action of the substance by surrounding it with albumen. 

When the blood is in large proportion there is alteration of the 
remedial action; when it is in small proportion there is, on the 
contrary, increase in the intensity of action ; and doses which, 
under certain weight, would not be poisonous for a vigorous sub- 
ject, may prove so for individuals in an anaemic condition. 

We will now commence the study of the complex influences 
which result from relation of age, sex, temperaments, races, mode 



SIZE OF DOSES. 431 

of life, and climate. You will see that the preliminary study 
into which we entered abridges the study of their relation. 

At any age, what is to be most regarded is the stature and 
bulk. You see that all I have just said to you concerning the 
size or bulk had its utility. I am well aware, however, that all 
of importance is not included under the conditions of weight 
and bulk, and frequently great consideration must be paid 
to influences due to other anatomical and physiological condi- 
tions. 

If we consider, for instance, infancy, we find special conditions 
which make infantile therapeutics differ considerably from the 
usual treatment in the adult. These are the physiological and 
anatomical conditions of the infant which cause differences in the 
doses. The infant has extreme susceptibility to impressions, 
which is the reason that the least excitation — a tooth pressing on 
the gum — induces spasmodic movements, which may indeed go 
as far as convulsions. Again, the infant has the cortical sub- 
stance of the brain of so marked vascularity that it is rose- 
colored, and might be thought to be inflamed, when the normal 
state is not known. An infant lives on an aliment which is in a 
bulky form, that is milk; the child is apt to take too much, and 
from time to time vomiting, regurgitation and diarrhoea occur. 
These three circumstances explain many particulars offered by 
infantile therapeutics: thus, you cannot give them substances 
stimulating to the nervous system without causing various acci- 
dents; they can safely inhale ethereal substances; if you lay them 
on a mass of hops, they sleep as if under the influence of an anaes- 
thetic; if you leave a bouquet of flowers in the room where a child 
is sleeping, they may have a toxic influence on it. In the same 
way, if you give a very young child a very small quantity of 
laudanum, accidents may follow; not only hypnotism, but pro- 
found, comatose stupor has been produced by two drops of lau- 
danum. 

There are also conditions which, in old age, cause variations 
in the action of medicaments. Thus, it is generally said that 
feebler doses are required for an old person. This is true, in 



432 PRINCIPLES AND METHODS OF THERAPEUTICS. 

general, but in certain cases they require larger doses than an 
adult, for example, to induce perspiration or to provoke purga- 
tion. 

As regards the sexes the difference is in great part due to the 
difference in weight, in the quantity of the blobd in circulation, 
and to the richness of the blood. 

In regard to the temperaments ; these are influences explained 
by conditions which we have already determined; thus the 
greater quantity of blood present in persons of the sanguine 
temperament, the greater feebleness or strength, etc. 

The predominance presented by certain organs should also be 
taken into consideration. Sometimes the nervous system is most 
predominant, and offers, in such cases, extreme susceptibility. 
Nervines should be given with precaution to such patients. 
Bilious people support purgatives very well, while others cannot 
tolerate them. 

Now a few words concerning the manner of life of the indi- 
vidual, his habits and occupations. 

Without speaking of occupations which may have some pecu- 
liar action, there are at least two great divisions to make : manual 
avocations and intellectual pursuits. Individuals leading a 
sedentary life become intolerant of most medicaments ; those 
who have the blood rich, in whom the functions are better regu- 
lated, often present a resistance which may be termed tolerance. 
This is why more considerable doses are required for people in 
the country than for inhabitants of a large city. 

Climatic influences are very complex ; heat, cold, aliments, the 
productions of the soil, all these conditions induce variations in 
the state of health, and even of temperament and constitution. 
Then, again, there are poisons of all sorts which may exist in one 
climate and not in another. Climate itself acts, in general, by 
causing subjects to become vigorous, or, on the contrary, sallow 
and weakly. In the north plethoric individuals are frequent, 
in the south the greater portion are anaemic. Certain organs are 
apt also to acquire predominance of action. In hot climates, we 
know that the hepatic apparatus is apt to become predominant, 



INFLUENCE OF CLIMATE. 433 

because there is imperfect combustion, and because most of the 
unconsumed materials are eliminated by the liver. 

All these circumstances induce corresponding differences in the 
activity of medicaments, and in the direction or predilection 
which remedial agents manifest for certain organs. 

I have already mentioned, in speaking of climates, the much 
greater capacity of the inhabitants of the north for alcoholic 
beverages. I could say to you, that general bleeding is better 
tolerated in the tropics than in the northern climates. It is on 
this account that the theories of Rasori had so much success in 
Italy and Greece ; more considerable success than with us, more, 
in particular, than they had in the north. 

I am myself an example of the utility of general bleeding. I 
fell once, in Italy, bathed in blood ; I was carried to the hospital 
of Milan, where they bled me, two, three, even four times per 
diem ; I was longer in recovering from the effects of the bleed- 
ing than from those of the wound. 

I have often asked myself whether, if these bleedings had not 
been made, I should not have had tetanus, in such a month as 
July. General bleeding is well tolerated in southern climates. 
It is true that it is badly tolerated in marshy districts, because 
the paludal miasma reduces the inhabitants of such countries to 
a state of ansemia. 

What should I say to you regarding the medical constitution 
reigning at any period ? Medical constitutions are, after all, but 
climatic conditions, for they are due to poisons originating in the 
soil under the influence of temperature, poisons which might 
with propriety be termed telluric. 

There are regions more favored by nature and at the same 
time more afflicted than the one in which we live, in this sense, 
that the natural productions are of more splendor, but the causes 
of death more numerous, giving rise to cholera, yellow fever, etc. 
Into such elements may be analyzed what is termed medical 
constitution, and which should be called nosogenetic constitu- 
tion. 

In regard to race, there are notable differences, as regards 



434 PRINCIPLES AND METHODS OF THERAPEUTICS. 

remedial action, between individuals of the different races which 
people the globe ; but positive facts are wanting. 

In 1869 I remarked that the black race, the negro, has great 
tolerance for wounds of the abdomen ; so much so that an im- 
postor will sometimes open his abdomen before a multitude, in 
order that on his recovery he may be considered an inspired be- 
ing, singled out by divine interposition. All those who have 
sufficient daring to do it recover. I warrant you that you could 
not do as much, and that if you plunged a knife into your abdo- 
men you would infallibly succumb to the wound. 

Dr. Thaly,* in a recent paper, establishes the fact that negroes 
support enormous doses of tartar emetic; that one gram per diem 
may be given to them without producing more effect than is ob- 
tained from five centigrams with us. 

There are also considerable differences, at the present time well 
recognized, between the different races, as regards the action of 
substances capable of inducing drunkenness. 

Thus with us, with the Caucasian races, and with Europeans 
in particular, alcoholic intoxication is mild, gay, amiable — there 
are exceptions, I am well aware — but there are races, such as the 
inhabitants of Java, of Borneo, of Sumatra, the Malays, in whom 
the effect of opium is gloomy, rendering them furious and mur- 
derous. A Malay can never become drunk without attacking 
individuals who have done him no ill. With us, on the contrary, 
the great proportion of drunkards are not at all dangerous. 

This is not the effect of climate acting on. the blood. The 
proof is that Europeans in the same countries, and the other 
races which inhabit India, do not suffer the same mania after 
taking alcohol. Even for drunkenness produced by other than 
alcoholic substances, you will find the fundamental difference 
which I have just indicated. No matter of what nature the poi- 
son, individuals of the Mongolian or Malay race become violent, 
quarrelsome, and manifest a desire to commit murder. 

Finally, in regard to what is called idiosyncrasy: is it necessary 
to believe that certain individuals have the special privilege of 
* Thaly ; Archives de Mtdecine Navale. 



IDIOSYNCRASY. 435 

reacting in a peculiar manner under the influence of a therapeutic 
agent, and so much so that there is no means of establishing any 
general rules? This is what empirical physicians desire to 
prove. No ; idiosyncrasy cannot be admitted. All the modifi- 
cations presented by individuals may be reduced to the condi- 
tions I have enumerated. Nevertheless, we are yet at a loss when 
we seek an explanation of the manifestations presented by cer- 
tain subjects; but the science of to-day is not that of to-morrow ; 
my science is not yours, and you will arrive at the comprehen- 
sion of these phenomena in a future more or less distant. 



INDEX 



Abscess 167 

Acetic acid, 58, 98, 144, 146, 239, 253, 

260. 
Acetone, 260. 
Aconite, 32, 49, 76. 
Aconitine, 45, 57, 76, 161, 169, 180, 

183, 184, 186, 189, 195, 197, 202, 

224, 244, 424. 
Aconitism, 186. 
Acupuncture, 208. 
Addison, 296. 
Aelius, 156. 
Air, 109, 113, 120. 
Albumen, 6Q, 82, 163, 166, 213, 218, 

247, 248, 251-259, 260-267. 
Albuminates, 31. 
Albuminaria, 47. 

Albuminoid substances, 67, 166, 247, 

248, 251. 

Alcohol, 33, 38, 48, 84, 164, 175, 209, 

211, 260, 357. 
Aldehyde, 260. 
Alga, 103, 176, 178, 202. 
Alimentary substances, 82. 
Alkaline bromides, 54. 

chlorates, 54. 

chlorides, 54, 243, 251-267. 

iodides, 54. 
Alkaloids, 32, 49, 55, 60, 162. 
Ailing, E., 89. 
Almonds, bitter odor, 191. 

oil of sweet, 23. 
Aloes, 81. 
Alteratives, 41. 
Alum, 251. 

Alumina sulphate, 123. 
Ammonia, 24, 100, 143, 151. 

sulphide, 249. 
Ampulla, 151. 
Amygdaline, 191. 
Amvl, nitrite of, 198. 
Anaemia, 45, 47, 110, 189, 231, 233. 



Anaesthesia, 85, 91, 106, 163, 241. 

Anesthetics, 56, 96, 108, 198. 

Anaeurism, 160. 

Analgesia, 182, 189. 

Aniline colors, 97, 138. 

Anasarca, 190. 

Anthrax, 200. 

Antiseptics, 239. 

Antizimics, 177. 

Antizimotics, 177, 239. 

Apomorphine, 61, 206. 

Aran, 82, 84. 

Arcachon, 125. 

Aristotle, 35, 221. 

Armand, 107. 

Arsenical fumigations, 99. 

preparations, 79, 206. 
Arsenic, 26, 41, 59, 66, 102, 235, 208, 

244, 256, 269-288, 289-300, 301-313, 

314^325. 
Arsenious acid, 26, 28, 54, 59. 
Arteriotomy, 224. 
Aspbyxia, 148, 235. 
Asthma, 98, 106, 109, 111. 
Atropism, 89, 94, 96, 193, 420. 
Atropine, 57, 62, 76, 94, 96, 143, 156, 

161, 165, 168, 169, 172, 193, 205, 240, 

244, 391, 415, 420, 423. 
Aurum redactum, 251. 
Ayello, Dr., 113. 

Barella, 285. 
Barium chloride, 255. 

sulphate, 255. 
Baryta, 54. 
Baths, 131, 136, 146. 

aromatic, 99. 

arsenical, 147. 

compressed air, 110. 

carbonic acid, 148. 

medicinal, 91. 

vapor, 99. 



437 



438 



INDEX. 



Belladonna, 70, 72, 89, 101, 150, 494, 
402. 

cigarettes, 106. 

extract, 82, 85, 90, 135, 148, 157. 
Behier, 82, 160, 178, 204, 216, 418. 
Bennett, 238. 
Benzoic acid, 58, 178. 
Benzoin gum, 98. 

Bernard, Claude, 45, 61, 73, 74, 95, 118, 
161, 166, 193, 253, 255, 262, 322, 342, 
394, 421. 
Berthelot, 43, 97. 
Berthollet, 252. 
Bert, Paul, 109, 114, 214, 220. 
Bile, 81. 
Bischoff, 213. 
Bismuth, 

sub-nitrate, 250. 

sulphide 249. 
Black, 59. 
Blisters, 150, 251, 258. 

ammoniacal, 151. 
Blondeau, 87. 

Blood, 21, 25, 198, 213, 216, 218-225, 
226—237 

cerum, 125, 163, 213-218-225. 

globules, 21, 192, 213, 218-225, 
226-237. 

letting, 225, 229. 

transfusion, 212-225, 230-237. 
curative, 233. 
palliative, 233. 
preventive, 233. 
repressive, 233. 
Bocker, W., 33. 
Bonjean, 161, 195. 
Bonnefin, Dr., 37. 
Bonnefoy, 339. 
Bonnet, 151. 
Borax, 177. 
Bouchardat, 62, 392. 
Boucheterre, 123. 
Boudin, 281, 308. 
Bouilland, 403. 
Bouisson, 82. 
Bourboule, 123, 125. 
Bourdon, Hipp., 177. 
Bourneville, 415. 
Boxwood, 75. 
Brignet, 83, 227. 
Brignet, 83. 

Bromo-hydric acid, 167. 
Bronchiae, 44. 
Bronchitis, 97, 121. 

tracheo, 101. 
Broth, 82, 163. 



Brouardel, 227, 232, 236. 
Brown-Sequard, 132, 216, 222, 233. 
Bujon, 126. 
Buxine, 75. 

Cabanis, 19. 

Cachexy, cancerous, 234. 
Cacodyle, 59. 
Cacodylic acid, 59. 
Caffeine, 165. 
Cahours, Andre, 60. 
Cajaput essence, 52. 
Calcareous phosphates, 296. 
Calcium chloride, 119. 

oxide, 244. 

tribasic arseniate, 41. 
phosphate, 41. 
sulphide of, 103, 119, 124 
Calomel, 133, 134, 136, 148, 164, 247. 

249, 251, 376. 
Camphor, 105, 143. 
Cancer, 21, 78. 

of tongue, 82. 
Cantharides, 52, 135, 150, 258. 
Cantharidine, 135, 150, 255. 
Cantharidism, vesical, 150. 
Canterets, 124. 
Capillary tubes, 24. 
Carbon, 55, 103. 

oxide, 198, 235. 

sulphide of, 145. 
Carbonates of the earths, 25. 
Carbonic acid, 36, 91, 105, 107, 112, 

148. 
Carcinoma, 21. 
Cardiac affections, 192. 
Carlsbad, 133. 
Carrots, 30, 74. 
Castor bean, 81. 

oil, 133, 240. 
Castoreum, 143. 
Cauterization, 31. 
Cerebric acid, 49. 
Charcoal, powdered, 24, 67, 97. 
Chatin, 287. < 
Chemical actions, 23, 24. 

combinations, 53. 

constitution, 57, 59, 62. 

structure, 53, 62. 
Chevreul, 355. 
Chloral, 71, 172, 2al, 425. 
Chlorhydrates of chlorides, 247. 
Chlorhydric acid, 243, 250, 254. 
Chlorine, 54, 56, 208, 255. 
Chloroform, 56, 72, 85, 91, 95, 145, 145, 
148, 161, 163, 172, 174, 184, 200, 2)1. 



INDEX. 



439 



Chlorosis, 234. 

Cholera, 105, 152, 165, 239. 

Chomel, 82. 

Chouppe, 179. 

Christison, 285, 346. 

Cicutine, 143. 

Cinabar, 148. 

Cinchona, 76, 81, 83, 167. 

extract, 87. 
Cinchonidine, 161, 194. 

bromodydrate, 167. 
Cinchonine, 167. 
Cinchona succirubra, 167. 
Citric acid, 166, 260. 
Climate, influence of, 433. 
Cloquet, 202, 207. 
Clysters, 82. 
Coca, 32, 34, 57. 
Cod-liver oil, 25, 41, 78, 205. 
Coffee, 32, 34, 57. 
Cold, 39, 132, 183, 243. 
Colic, 132. 
Colin, 95, 290. 

Collapse, 82, 174, 179, 213, 235. 
Collin, 218, 229. 
Collodion, cantharidized, 153. 
Colocynth, 81. 
Colophony, 246. 
Coma, 87, 154, 199. 
Conicine, 143, 169. 
Conin, 143, 169, 184. 
Constipation, 133. 
Continho, Dr., 192. 
Convulsions, 60, 73, 173, 184, 217, 232, 

238. 
Copaiba, 52. 
Copper, 54, 166, 248. 

sulphate, 208. 
Correlation of forces, 34, 42. 
Coryza, 129. 
Cotton, raw, 151. 
Courty, 160. 
Creosote, 164, 206. 
Croton oil, 133, 134, 156, 161, 163. 
Crum-Brown, 60. 
Curara, 61, 74, 161, 168, 193. 
Curarine, 162, 160, 193. 
Cyanhydric acid, 25, 54. 
Cyanosis, 112. 

Datura, 101. 

cigarettes, 106. 
Daturine, 94, 169. 
De Graep, 160. 
Delioux de Savignac, 248. 
Delirium, 96. 



Delore, 130.. 

Demarquay, 85, 89, 91, 117, 335. 

Denys, 225, 234. 

Descartes, 310. 

Desgranges, 216, 227, 229. 

Devay, 216, 227, 229. 

Dextrine, 58. 

Diabetes, 

albuminous, 47, 203, 234. 

saccharine, 47, 203, 234. 
Diabetic, 58. 
Diarrhoea, 148, 250. 

Cochin China, 181. 
Dieffenbach, 213. 
Dieulafoy, 190. 
Digitaline, 75, 161, 388. 
Digitalis, 57, 155, 388, 391, 399, 411. 
Diphtheria, 175. 
Doctrine of signs, 30. 
Dolbeau, 227. 
Donders, 68. 
Doses, size of, 429. 
Douche, 121, 123, 126. 
Dropsy, 189. 

Duboisia myoporoides, 57. 
Duboisine, 57, 94, 143, 169, 417. 
Duchaussoy, 239. 

Duchenne (of Boulogne), 26, 285, 315, 
Dujardin-Beaumetz, 359. 
Dumas, 177, 213, 215, 216, 293. 
Dupuytren, 82, 210, 235. 
Duquesnel, 161. 
Durozier, 390. 
Dutrochet, 178. 
Dynamic actions, 23, 32. 
Dynamite, 55. 
Dynamizing effects, 27, 31. 
Dynamopliores, 34, 40, 57. 
Dysentery, 86. 
Dyspepsia, gastric, 80. 
Dyspnoea, 107, 112, 118, 121. 
Dysuria, 258. 

Earthy carbonates, 97. 
phosphates, 97. 
Eczema, 147. 

Electricity, 18, 36, 43, 174, 208. 
Electro-puncture, 208. 
Emboli, 68, 217, 224, 230, 241, 251. 
Emetics, 206, 239, 412. 
Emetine, 52, 161, 207. 
Emphysema, 200. 
Emulsine, 191. 
Endometritis, 126. 
Endotherniic substances, 27, 32. 
Enghien, 124. 



440 INDEX. 




Epididymis, 211. 


Gamboge, 81. 




Erasistrates, 19. 


Gangrene, 166, 209. 




Erethism, 108. 


Gasparin, Count Agenor de, 32. 




Ergot, 45, 195, 424. 


Gastric mucous membrane, 47. 




Ergotine, 44, 161, 168, 184, 195. 


Gayon, 152. 




Ergotinine, 161. 


Gerard, 150. 




Erythema, 200. 


Gerhart, 143. 




Eschars, 135, 151, 163, 178, 210. 


Gesellius, 224. 




Escnline, 75. 


Gingival line, 68. 




Eserine, 94, 169, 415. 


Giraud-Teulon, 216. 




Esophageal spasms, 78. 


Globules, 25, 35, 113, 192, 214, 216, 




Ether, 48, 72, 145, 161, 163, 184, 200. 


226, 230, 236. 




nitrous, 58. 


Glucosides, 55, 162. 




Ethyl, 60. 


Gluten, 166, 248. 




nitrite, 58. 


Glycerine, 152, 164, 178. 




Ethylostrychnium, 60, 162 


Glycocol, 58. 


• 


Eucalyptus branches, 106. 


Glycose, animal, 58. 




essence of, 52. 


vegetable, 58. 




hydrolate, 178. 


Glycosides, 32, 75. 




Eulenburg, 191. 


Gobley, 49, 118, 293. 




Excitants, 44. 


Gold, 79, 248. 

oxide, 251. 




Fabre\ 208. 


Gondret's ointment, 151. 




Fabricius, 238. 


Gosselin, 46, 178. 




Fecamp, 125. 


Gout, 47, 125. 




Fereol, 227. 


Grsefe, Von, 417. 




Ferments, 80, 33, 195, 243. 


Gratiolet, 117. 




Ferric chloride, 117, 118. 


Guaco, 427. 




sulphate, 117. 


Gubler, 292, 322. 




Fever, 126, 194, 239, 254. 


Guillot Natalis, 288, 330. 




afternoon, 167. 


Gum, 55, 58. 




hectic, 203. 


arabic, 247. 




paludal, 9c. 


Gun cotton, 29. 




traumatic, 101. 


Guyochin, 29. 




typhoid, 203, 250. 






Fibrine, 230, 258. 


Hsematosis, 130, 219, 254. 




Fistulas, 71, 128. 


Hsemoglobine, 25, 213, 220. 




Flourens, 421. 


Haller, 132. 




Foetus, 51. 


Hardy, 283. 




Forges-les-Bains, 249. 


Harley, John, 418. 




Formic acid, 143. 


Heart disease, 112, 199. 




Foutan, 103. 


lesion of, 111, 112. 




Fourcroy, 111, 158, 262. 


Heat, 38, 132, 243. 




Frankincense, 98. 


Hebert, 136. 




Fraser, Thomas, 60, 416. 


Helminths, 133. 




Frazer, 208. 


Hemapheine, 49. 




Friederichshall, 134. 


Hematics, 219. 




Fremy, 49, 


Hematuria, 150. 




French blue, 253. 


Hemlock, 150. 




Frictions, mercurial, 148. 


Hemorraphylia, 234. 




Fulminates, 28. 


Hemorrhage, 196, 199, 202, 221, 231. 




Fumigations, arsenical, 148. 


235, 250. 




mercurial, 148. 


Hemorrhoids, 100. 




sulphurous, 148. 


Henry, Ossian, 117,. 119. 
Hepatic parenchyma, 27. 




Gaevin, 87. 


Hering, 192. 





INDEX. 



441 



Hippocrates, 150. 

Hirtz, 139. 

Histological elements, 25, 27. 

Homoeopathy, 20. 

Hops, 56. 

Horse-chestnut bark, 75. 

Hottot, 161. 

Humboldt, 226. 

Hunter, Charles, 160. 

John, 51, 63, 131, 188. 
Hydrargyrism, 128, 149. 
Hydro-carbons, 56, 58, 106. 
Hydrochloric acid, 146, 205, 251. 
Hydrogen, 55, 60, 93, 245. 

arseniated, 102. 

phospiiuretted, 246. 

sulphuretted, 95, 102, 124, 245, 
249, 259. 
Hydro-therapeutics, 20. 
Hyperemia, 45, 121. 
Hyperesthesia, 182, 183. 
Hypnotics, 184. 
Hypochlorites, 54. 
Hypochlorous acid, 255. 
Hypodermic, 70, 178. 

injections, 163, 179, 205, 209, 
240. 

method, 155, 157, 160, 191, 195, 
199, 293, 207. 

solutions, 168. 
Hyposulphites, 54, 150. 
Hyposulphuric acid, 121. 
Hyposulphurous acid, 121. 
Hypothermesthesia, 183. 

Icterus, 30. 
Idiosyncrasy, 434. 
Inanition, 235. 
Indigestion, 206. 
Indigo, urinary, 138. 
Infarcts, 218, 230, 241. 
Infection, prevalent, 231. 

syphilitic, 231. 
Inflammation, 63, 178, 202, 210, 211. 
Influenza, 192. 
Injection, 179, 248. 

intravenous, 212, 228, 239. 

venoso-venous, 228. 
Ink, 117, 118. 
Innocent VIIL, 212. 
Iodine, 71, 79, 85, 89, 97, 121, 140, 208. 

tincture of, 71, 129, 142, 209, 
210, 211. 
Iodism, 71, 129. 
Ipecac, 52, 98, 207, 404. 
Iron, 25, 41, 46, 54, 78, 79, 206, 244, 245. 



lactate, 253. 

oxide, 244, 251. 

perchloride, 93, 117, 121, 160, 
206, 248. 

peroxide. 123. 

sulphate, 117, 252. 

sulphide, 249. 
Ischemia, 45. 
Isomeric bodies, 58. 
Isomorphous, 59. 

Jaborandi, 192, 427. 

Jaccoud, 285. 

Jalap, 81, 84. 

Jamin, 116 

Jobert de Lamballe, 211. 

Jolyet, 60. 

Jourdanet, 110. 

Kaufmann, 213. 
Kissingen, 107, 133, 148. 
Kolliker, 63. 
Kreuznach, 128. 

Laborde, 299, 339. 

Labor, 221, 235. 

Lactic acid, 243, g45, 250, 251. 

Laennec, 111. 

Lafarge case, 318. 

Lafargue de Saint-Emiline, 70, 155, 

158. 
Lallemand (of Montpellier), 35, 127 

208, 221, 353. 
Lambert, 150. 
Langenbeck, 158. 
Laudanum, 194, 239, 403, 419. 
Laryngitis, chronic ulcerated, 123. 
Law, 384. 

Lead, 248, 388, 394. 
Lecithin, 49. 
Legumine, 166, 248. 
Lepine, 322. 

Leptonitus sulphuraria, 104. 
Lemon essence, 58. 
Lesneur, 150. 
Levain, 227. 
Leucorrhoea, 90. 
Libavius, 212. 
Liebig, Justus, 49. 
Liebreich, O., 49, 293. 
Life-awakener, 157. 
L'hote, 318. 
Lime, arscni;ite of, 46. 

carbonate, 119, 244. 
hypophosphate of, 59. 



442 



INDEX. 



Lime, sulphate, 103, 119. 
tri-arseniate of, 59. 
Limousin, 112, 178, 262. 
Linden, 101. 
Linnaeus, 22. 
Lypothymia, 235. 
Loueche, 102. 
Lower, 212. 
Luchon, 124. 
Luer, 162. 

Lutton, 70, 163, 209, 211. 
Lycopodium powder, 254. 
Lymphangitis, 258. 
Lymphatic ganglions, 209. 

Madder, 138. 

Magendie, 95, 213, 215, 238, 372. 

Magnesia, calcined, 244. 

carbonate, 244. 

sulphate, 119. 
Maissonneuve, 227. 
Manganese, 41, 46, 78, 244. 
Marcy, 416. 

Marsh mallow root, 84, 92. 
Mate, 32. 
Mathieu, 229. 
Mayer's hammer, 151. 
Medicament, 18, 23, 44, 53, 62. 
Medicinal infusion, 238. 
Melsens, 256, 288, 330, 392. 
Meningits, 206. 
Mensonides, 68. 

Mercurial salts, 166, 173, 177, 184, 201. 
Mercury, 23, 54, 69, 79, 134, 148, 161, 
165, 166, 343. 

bichloride, 209, 247. 

proto-chloride, 166, 247, 249. 

proto-iodide of, 72, 249. 

sulphide, 100. 
Methyl, 60, 162. 
Meyer, 68. 

Mialhe, 66, 154, 247, 254, 260. 
Miasma, marsh, 29. 
Milk, 72, 163. 

Milne-Edwards, Alphonse, 46. 
Milne-Edwards, 235. 
Mineral nymphs, 125. 
Montecoro, 191. 
Moreau, 133. 

Morphine, 57, 60, 62, 107, 146, 151, 
154, 156, 165, 169, 179, 184, 
186, 189, 190, 194, 198, 240, 
244, 359, 423. 

chlorhydrate of, 165. 

syrup of, 154, 194. 
Morphinsim, 90. 



Mouvout, 81, 169. 
Mucedina, 176. 
Mucilages, 22. 
Mucilaginous injections, 92. 
Muscles, 32, 35, 37, 44. 
Mydriasis, 89, 94, 172, 416. 
Myeline, 49. 
Myosis, 416. 
Myotility, 35. 

Naevi, vascular, 156. 

Narcosis, 184, 194, 232, 241. 

Narcotism, 94, 96. 

Nekton, 211. 

Nephritis, 150. 

Nervine, 46. 

Nervous system, 32. 

Neuralgia, 163,181, 185, 202, 211, 224. 

Neuralgias, congestive, 190. 

ileo-lumbar, 154. 

of fifth pair, 72, 184. 

of neck of bladder, 90 
Neurility, 35. 
Newman, 143. 
Nicotine, 143, 146, 159. 
Nitrates, 28. 
Nitre, 107. 

Nitric acid, 83, 85, 138, 260. 
Nitrogen, 28, 55, 57, 62, 107, 120, 177. 
Nitrous oxide, 107. 
Node, 201. 
Normand, 181, 194. 
Nux vomica, 150, 385. 

Oil, 246. 

Oliguria, 258. 

Orange leaves, 101."' 

Ore, 240 

Orezza 249. 

Opium' 32,'45, 49, 70, 82, 86, 87, 150, 

184, 199, 370, 394, 402. 
extract, 107, 159. 
Orfila,82, 287, 291, 327. 
Organisms, 21. 
Ornella, 161. 
Osteomalacia, 46. 
Osterlein, 68. 
Overbeck, 301. 
Ovid, 212. 
Oxalic acid, 54. 
Oxygen, 26, 36, 54, 55, 75, 107, 109, 

111, 114, 120, 216, 219, 223, 245, 255, 

260. 
Ozone, 29, 114. 

Pancreatine, 80, 81. 



INDEX. 



443 



Paper, nitrified, 106. 
tarred, 105. 

Paralvsis, 36, 46, 50, 61, 80, 201, 220. 
* of the bladder, 93. 

of the vocal ligaments, 118. 
Paul, Constantin, 164. 
Pavie, 215. 
Pepsine, 163, 243. 
Peptones, 163. 
Percussion, 121. 
Pereira, 255. 
Peritonitis, 92, 134. 
Perrin, 260, 253. 
Personne, 244, 248. 
Petit, 57, 143. 
Phenic acid, 178, 206, 241. 
Phlebitis, 231, 258. 
Phlegmons, 166, 206. 

gangrenous, 203. 
Phlogosis, 209. 

Phosphates of the earths, 25, 46. 
Phosphoric acid, 75, 243, 245, 251. 
Phosphorous, 26, 41, 45. 66, 75, 79, 
198, 208, 245, 249. 

acid, 75, 246. 

preparations of, 206. 
Phthisis, 97. 

tubercular, 30. 
Picrotoxin, 57, 94, 161, 184, 201. 
Pidoux, 247. 
Pierrefonds, 124. 
Pigeaux, 126. 
Pills, 81, 242, 380. 
Pilocarpine, 191. 
Pilocarpus pennatifolius, 192. 
Pindarus, 20. 
Pine branches, 106. 
Pirogofi; 85. 
Plasma, 25, 27. 
Plasmine, 25, 215, 218. 
Platinum, 248. 
Planchud, 103, 273. 
Plumb, 95. 
Pneumonia, 

broncho, 121. 
Poggiale, 118. 
Poisenille, 215. 
Polysarcia, 47. 
Poppy, 92, 101. 
Potain, 20, 190. 
Potash carbonate, 215, 244. 

chlorate, 256. 

chloride, 52. 

iodide, 257. 

nitrite, 107, 205, 215. 



Potash, salts, 47. 

sulphate, 260. 
Potassium bromide, 24, 252, 426. 

chloride, 166. 

cyanide, 117, 138. 

ferrocyanide, 118, 137, 253. 

iodide, 24, 26, 85, 90, 91, 96, 
135, 139, 141, 184, 256, 426. 

and iron (vellow prussiate), 74, 
191. 
Poultices, 64, 131, 135, 146. 
Powell, Dr., 113. 
Pravaz, 70, 160. 
Presi, Nicholas, 107. 
Prevost, 213, 215, 216. 
Protagon, 49. 
Prussian blue, 139, 253. 
Puerperal affections, 203. 
Pullna, 133. 
Pulmonary, 30. 

rupture, 200. 
Purgation, 133. 
Purgatives, 239. 
Purpura, 234. 
Pustules, 135. 

Quetelet, 428. 
Quevenne, 389. 
Quinetum, 167. 
Quinicine, 29, 198. 
Quinidine, 29, 198. 

Quinine, 29, 57, 60, 76, 83, 126, 156, 
161, 165, 167, 184, 193, 195, 
198, 244, 254, 359. 
b»omohvdrate, 126, 161, 168, 

181, 194, 201. 
mono-bromhydrate of, 164. 
sulphates of, 29, 77, 83, S6, 87, 
125, 164, 194, 199, 201, 239, 
342. 
bi-sulphate, 83, 165. 
Quinoidine, 169. 

Kavel, eau de, 83. 
Rabuteau, 133, 262. 
Rachitis, 46. 
Rasori, 398. 
Raspail, 105, 313. 
Rapon, 100. 

Raynaud, Maurice, 227. 
Regnault, 111. 
Re i set. 111. 
Resinates, 246. 
Reveil, 1«»7. 

Rheumatism, blennorrhagic, 93. 
nodular, 447. 



444 



INDEX. 



Khubarb, 134, 138. 
Kichet, 93, 127, 227. 
Rieord, 289. 
Kiotinto, 123. 

Robin, Charles, 25, 146, 178. 
Eoussel, 216, 228. 
Roussin, 149. 
Royat, 125. 

Saint Alban, 148. 
Saint Honore, 124. 
Saint Nectaire, 125. 
Sales-Girons, 115, 117. 
Salicylic acid, 178, 377. 
Salins, 128. 
Salis de Beam, 128. 
Salivation, 192. 
Sandras, 346. 
Sanguinarine, 61. 
Saturnine paralysis, 26. 
Sammony resin, 84, 136. 
Scarlatina, 137. 
Scheel, 238. 
Schiff, 132. 

Sciatica, 173, 184, 208, 211. 
Sciatic pains, 159. 
Scoutetten, 28, 147. 
Scrofula, 21, 125, 128. 
Scurvy, 202, 234. 
Sedlitz, 133. 
Segalas, 86, 335. 
Seguin, 132, 135. 
Septic diseases, 234. 
Sequela?, 128. 
Sideration, 226. 
Silica, 97. 
Silver, 248. 

albuminate, 212. 

chloride, 242, 247, 252. 

metallic, 242. 

nitrate, 93, 121, 123, 126, 209, 
211, 242, 247, 252. 
Simpson, 262. 
Sinapism, 63, 147. 
Soemmering, 132. 
Soda, 105, 260. 

arseniate, 123, 146. 

bicarbonate, 239, 246, 250, 255. 

carbonate, 25, 146, 244, 251. 

hypochlorite, 255. 

phosphate, 215, 254. 

sesqui-carbonate, 115. 

sulphate, 27, 53, 215, 239, 254. 
Sodium, chloride of, 66, 115, 166, 210, 
239, 247, 252. 

sulphide, 124. 



Spa, 249. 

Spasm, 121, 123, 173, 232, 238. 

Spasms esophageal, 82. 

Starch, 55, 58, 68, 85. 

Steatosis, 296. 

Stomatitis, 69, 90, 128. 

ulcerous, membranous, 52. 
Straus, 227. 

Strychnine, 38, 44, 45, 49, 60, 73, 82, 
87, 96, 162, 165, 169, 184, 189, 239, 
385. 
Strychnos castellana, 61. 

colubrina, 61. 

toxifera, 61. 
Stupor, 184. 
Substitution, 209. 
Sugar, 55. 

diabetic, 58. 

grape, 58. 
Sulphates, 120. 

Sulphur, 26, 41, 66, 102, 120, 245, 249, 
260. 

liver of, 102. 
Sulphuraria, 104. 

Sulphuric acid, 165, 205, 245, 254, 260. 
Sulphurous acid, 245. 
Suppositories, 82. 
Sweat, 25, 192. 
Syncope, 174, 179, 226. 
Syphilis, 72, 128, 134, 148, 149, 175. 
Syphilitic lesions, 69. 
Syringe, 161, 168. 
Syrups, 382. 



Tabes, 46. 

Tannin, 24, 117, 121, 133. 

Tar, 105. 

Tardieu, 97. 

Tartar emetic, 135, 161, 206, 399, 434. 

Tartaric acid, 166. 

Tattooing, 68. 

Taylor, 274. 

Tea, 32, 34, 57. 

Temperature, 121, 125, 243. 

Tetanus, 60, 73, 101, 238, 241, 277, 422. 

Thaly, 434. 

Thenard, 114. 

Thenard, P., 114, 294, 318. 

Therapeutics, 18. 

Theresa, Saint, 129. 

Thermo-therapeutics, 20. 

Thrombus, 217, 231. 

Thrush, 178. 

Tinder, 106. 

Tissue-saving foods, 33. 



INDEX. 



445 



Tobacco, 94, 394. 

leaves, 135. 

seed, 254. 
Tonics, 38, 44. 
Tracheotomy, 118. 
Trismus, 78, 82. 
Trophoneurosis, 202. 
Trousseau, 24, 25, 65, 70, 72, 76, 92, 
121, 151, 156, 210, 224, 247, 382, 385. 
Trouville, 125. 
Tschudy, 278. 
Tubercles, 110. 

mucous, 128. 
Tuberculosis, 110, 203. 
Tube-roses, 56. 
Tumor, 156, 160, 210. 
Tumors fungous, 83. 

hemorrhoidal, 84. 
Turpentine, 52, 56, 106, 260. 

Ursemia, 234. 
Urea, 224, 234. 
Urethritis, 93. 
Uriage, 124. 
Urticaria, 181, 201. 
Ussel, 124. 
Uterine myomata, 209. 

Vaccination, 156, 175, 230. 

Vaccine, 21, 156, 230. 

Vaginismus, 90. 

Valerianic acid, 143. 

Vals, 107, 124, 260. 

Vanillin, 178. 

Van Swieten's solution, 72, 90. 

Vella, 161, 422. 

Vena cava, 161. 

Venous system, affection of, 161. 

Veratrine, 169, 184. 

Vertigo, 114. 

Vichy, 107, 124. 

water, 25, 76, 115, 255, 260. 



Vilate, liqueur de, 1 24. 

Villemin, 98. 

Vinegar, 100. 

Volvulus, 23. 

Vomiting, incoercible, 87, 235. 

incurable, 82. 
Vulpian, 45, 132, 217, 266, 422 

Waller, 226. 

Water, 96, 98, 100, 138, 146, 163, 189, 
190, 238, 243, 245, 260. 

arsenical, 102, 124. 

atomized, 119, 120, 123. 

bay-cherry, 178. 

bituminous, 124. 

distilled, 92, 93, 115, 164, 181, 
189. 

iodo-bromized, 128. 

javel, 255. 

mineral, 102, 108, 119, 120, 123, 
125, 133, 146. 

saline, 124. 

salt, 93. 

sea, 125. 

sulphur, 124. 

sulphurous, 95, 102, 1 19, 124. 
Waters, alkaline, 124. 
Willemin, 139. 
Wine, 82. 

Woehler, 256, 260, 255. 
Wood, Alexander, 160, 175. 
Woorara, 422. 
Wounds, burrowing, 128. 

Yvon, 195. 

Zinc, 248. 

chloride, 205, 250. 
oxide, 205, 244, 250. 
phospbide, 80. 
sulphide, 249. 



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2 



THE MODERN 

T herapeutics S erTes 



EDITED TO 1880. 

1.— MODERN MEDICAL THERAPEUTICS. A Compendium of 
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IN THE MEDICAL THERAPEUTICS the total number of authors 
quoted is 723, and the precise formulae given, 1124. Each disease is taken 
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IN THE SURGICAL THERAPEUTICS the number of authors 
quoted is 418; the number of their prescriptions given, 1008. The spe- 
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collect in one volume the Therapeutics of Surgery, the formulae and 
medical treatment of Surgical diseases of the most eminent surgeons. 

3 



THE THERAPEUTICS OF GYNECOLOGY AND OBSTETRICS 

presents a condensed, carefully weighed and accurately presented review 
and estimate of the therapeutical resources of the gynaecologist and 
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press and all the special journals of both continents have been laid 
under contribution. 



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"This is a useful and interesting book, which no one can take up without finding something he 
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and Circular (London), September, 1880. 

"This work is well conceived and carefully executed, and will be of very great service to the 
practitioner." The Lancet, London, August, 1879. 

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As a means of familiarizing with the methods and remedies employed in different parts of the world 
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"Divested as they are of all that is not strictly practical, containing such information as is of 
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practitioner particularly will find of great assistance." — Michigan Medical News, March, 1880. 

"Give a practitioner these three volumes, and one or two good journals, and he needs little else, 
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"An admirable compendium * * * an eminently practical work." — Michigan Medical News. 

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The following opinions refer to the Therapeutics of Gynecology 
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Medical News, March, 1880. 

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March, 1880. 

"We recommend it as filling a general want."" — Atlanta Medical and Surgical Journal, 
February, 1880. 

4 



A BIOGRAPHICAL DICTIONARY 

OF 

CONTEMPORARY AMERICAN PHYSICIANS 

AND 

SUBGEOITS. 



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material. 



THE PRINCIPLES AND METHODS 

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5 



DIFFERENTIAL DIAGNOSIS: 

A MANUAL OF THE COMPARATIVE SEMEIOLOGY OF THE 
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By DE HAVILLAND HALL, M.D., 

Assistant Physician to the Westminster Hospital, London. 

Second American Edition, with Extensive Additions. 
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LESSONS IN GYNECOLOGY. 

BY WM. GOODELL, A.M., M.D., 

Professor of Clinical Gynaecology in the University of Pennsylvania. 

SECOND EDITION. 

THOROUGHLY REVISED AND CONSIDERABLY ENLARGED, WITH 
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value is its practicalness. Little points of detail teem up on almost every page, showing that it is 
the work of a man who has often done what he wishes his readers to do.*' — Glasgow Medical Jour- 
nal, November, 1880. 



COMMON MIND-TROUBLES, 

AND 

THE SECRET OF A CLEAR HEAD. 

By J. MORTIMER-GRANVILLE, M.D., F.R.G.S., LONDON, etc. 

One Vol., Crown 8vo, Cloth, pp. 185. Price $1.00. 



Reprinted from the Eleventh thousand of the London Edition, with 
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CONTEXTS. 
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Morbid Fears — " Creatures of Circumstance." 

PART II. Temperature — Habit — Time — Pleasure Self-import- 
ance — Consistency— Simplicity — The Secret of a Clear Head. 

7 



Atkinson. Hints on the Obstetric Procedure. 8vo. Cloth, $1.00. 

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HYDROPHOBIA, 

.A. Monograph for tlie Profession and. the IPnolic, 

ByH. R. BIGEL0W, M.D. 

FR-ICE, CLOTH, &JL.OO. 



This treatise, the outcome of several years' study of this terrible 
complaint, will contain the latest investigations into its pathology, 
causes, communicability, proguosis, prophylaxis and treatment. 

8 



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